Please cite this article in press as: Szuplewska et al.

, Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in

Biotechnology (2019), https://doi.org/10.1016/j.tibtech.2019.09.001

Trends in Biotechnology

Review
Future Applications of MXenes in Biotechnology,
Nanomedicine, and Sensors
Aleksandra Szuplewska,1 Dominika Kulpi nska,1 Artur Dybko,1 Michał Chudy,1,*
Agnieszka Maria Jastrze˛bska,2,3,* Andrzej Olszyna,2 and Zbigniew Brzózka1

The past few years have seen significant developments in the chemistry and potential biological Highlights
applications of 2D materials. This review focuses on recent advances in the biotechnological and 2D carbides have been applied as
biomedical applications of MXenes, which are 2D carbides, nitrides, and carbonitrides of transi- highly efficient and selective
tion metals. Nanomaterials based on MXenes can be used as therapeutics for anticancer treat- agents for photothermal therapy
ment, in photothermal therapy as drug delivery platforms, or as nanodrugs without any addi- both in vitro and in vivo.
tional modification. Furthermore, we discuss the potential use of these materials in biosensing
The outstanding electrical and op-
and bioimaging, including magnetic resonance and photoacoustic imaging techniques. Finally,
tical parameters of MXene mate-
we present the most significant examples of the use of MXenes as efficient agents for environ-
rials make them interesting candi-
mental and antimicrobial treatments, as well as a brief discussion of their future prospects and dates for sensing applications.
challenges.
3D MXene phases can be used
as sorptive and antimicrobial
MXenes as Novel Nanomaterials for Biological and Environmental Applications
materials.
Recently, there have been significant advances in the chemistry of 2D materials such as graphene and
graphene-derived structures [1]. Currently, graphene and graphene-containing nanocomposites are
commonly applied in many fields such as electronics, sensors, and catalysis [2,3]. The unique physi-
cochemical properties of these materials [e.g., near-infrared (NIR), absorption and high surface-to-
volume ratios] are also interesting for biological applications [4–8].

Earlier reviews have discussed the utility of a new class of 2D materials, MXenes (see Glossary), as
novel bioactive agents which can be applied in anticancer therapies and bioimaging [9–12]. MXenes
are a family of carbides, nitrides, and carbonitrides that contain transition metals (mainly from groups
3 and 4) and are characterized by unique morphologies and outstanding catalytic (e.g., photothermal
and electrochemical) performance (Boxes 1 and 2) [13–15], that is usually much better than other
commonly applied nanomaterials such as graphene, gold (Au) nanorods [e.g., photothermal conver-
sion efficiency, h, for graphene was
56% vs >81% for polyethylene glycol-modified (PEGylated) 2D
Ti2C MXene] [16], or tungsten and hydrogen sulfides [17,18]. In this review we focus on MXenes as
novel materials for various bioapplications (Figure 1). We demonstrate the leading examples of these
materials as applied in biological systems, including their potential for use as antimicrobial agents
and in water purification systems. In comparison with previous reviews on MXenes, we stress that
similar studies can potentially lead to ambiguous conclusions (e.g., studies on MXene antimicrobial
properties). Moreover, we present exemplary data to stimulate scientific discussion on the standard-
ization of synthetic and bioanalytical protocols.

Bioimaging Based on MXenes 1Faculty of Chemistry, Warsaw University

of Technology, 00-664 Warsaw,

Fluorescence microscopy is one of the most widely applied bioimaging techniques in bioresearch Noakowskiego 3, Poland
owing to its ease of use and the inexpensive equipment required. Thus, it is very convenient to use 2Faculty of Materials Science and

this technique for bioimaging, despite its low penetration depth (e.g., ca 1500 mm in a thick grey mat- Engineering, Warsaw University of
Technology, 02-507 Warsaw, Wołoska 141,
ter medium under three-photon excitation) [19]. Generally, ‘traditionally’ prepared MXenes exhibit
Poland
low luminescence in aqueous solutions [20], but it is possible to enhance their fluorescent properties. 3www.inmat.pw.edu.pl/Badania-i-
One of the leading strategies to accomplish this is based on attaching a fluorescent species to the nauka/Grupy-badawcze/Bioaktywne-
surface of MXenes. Liu and coworkers described the generation of Ti3C2 loaded with the fluorescent nanomaterialy-o-strukturze-2D-
krysztalu
drug doxorubicin (DOX) and hyaluronic acid (HA) for tumor targeting [21]. Conjugates were obtained
*Correspondence:
by the electrostatic layer-by-layer adsorption of Al oxyanion-terminated MXene and cationic DOX. In
chudziak@ch.pw.edu.pl,
addition to bioimaging, the system could also be used in anticancer therapy [21]. agnieszka.jastrzebska@pw.edu.pl

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ª 2019 Elsevier Ltd. All rights reserved.
 Please cite this article in press as: Szuplewska et al., Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in
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Box 1. MXenes: Brief Preparation Methods

Glossary
MXenes (Figure I) are a novel group of interesting 2D materials composed of layered transition metal carbides, MAX phase: a substrate for
nitrides, and carbonitrides. The MXene family of materials has rapidly expanded since their discovery in 2011 MXene synthesis characterized by
[108]. The parent materials are MAX phases with the chemical formula Mn+1AXn, where M is a transition metal, the chemical formula Mn+1AXn,
A is a group A element, and X is a carbon or nitrogen, n = 1–3, and is composed of A layers sandwiched within where M is a transition metal, A is
octahedral Mn+1Xn [109]. The Mn+1Xn structure is obtained by selective acidic etching of A layers. The pioneer- a group A element, X is carbon or
nitrogen, and n = 1–3, that is
ing experiment of Ti3C2Tx synthesis involved the removal of Al from the Ti3AlC2 MAX phase using an aqueous
composed of A layers sandwiched
solution of hydrofluoric acid (HF) as the etchant. The presence of Tx terminal groups on their surface (i.e., Tx =
within octahedral Mn+1Xn.
OH, O, and F) occurs as a result of a series of chemical reactions between the MXene surface and HF. In the next MXenes: a novel family of 2D
step, ultrasonic delamination is carried out which allows single- or few-layered MXenes to be obtained [108]. materials composed of carbides,
This typically involves additional intercalation with large cations such as tetramethylammonium (TMA+) or tet- nitrides, and carbonitrides of
rabutylammonium (TBA+), which makes the process more efficient. Such a strategy is used in the synthesis of transition metals, mainly titanium.
most 2D MXene sheets from Al-containing MAX phases. Later on, more sophisticated procedures were devel- Photodynamic therapy (PDT): a
oped to replace the hazardous HF, and these employed ammonium bifluoride and other fluoride salts, which method based on the administra-
form HF in situ during these Mn+1AXn etching processes. Subsequently, a high-yield, milder method was devel- tion of a photosensitizing agent
followed by irradiation at a proper
oped to prepare 2D Ti3C2Tx by using LiF and HCl solutions and mild shaking. The resulting 2D flakes contain
wavelength corresponding to an
fewer nano-defects and have larger lateral dimensions [52]. Additional details on the chemistry of MXenes are
absorbance maximum of the
given in an excellent review article by Wang and coworkers [110]. sensitizer. Local inflammation
then leads to destruction of
abnormal cells. PDT can be used
to treat some types of cancer as
well as some other dysfunctions of
light-accessible tissue and
organs.
Photothermal therapy (PTT): a
physicochemical, almost nonin-
vasive, anticancer therapeutic
procedure based on the use of
photothermal agents and optical
radiation in the NIR wavelength
range (700–2000 nm) to generate
local hyperthermia leading to
denaturation of proteins, cytosol
evaporation, and cell membrane
lysis, leading to cell death.
Synergistic effect: the interaction
between two or more modalities
resulting in a more efficient effect
of simultaneous treatments in
comparison with each therapy
applied separately.

Figure I. MXene Chemistry. This figure depicts the synthesis of MXenes from exemplary MAX phases.
Reproduced, with permission, from [111].

Xue and colleagues [22] prepared Ti3C2 MXene-derived quantum dots (MQDs) by cutting the nano-
material. The resulting MQD diameter was dependent on the reaction temperature (2.9–6.2 nm for t =
100–150 C; the average MQD thickness was <1 nm). Similarly to other carbon-based fluorescent
nanomaterials (e.g., graphene QDs [22]), the photoluminescence spectrum of MQDs is excitation-
dependent. As the absorption shifts from the UV (340 nm) to the visible range (440 nm), the photo-
luminescence emission maximum shifts from blue to red, and two types of such MQDs were tested
for in vitro bioimaging [23]. Another attempt to perform MXene-based bioimaging was presented
by Wang and coworkers [24] who used a delamination reaction in aqueous tetramethylammonium hy-
droxide and subsequent sonication to obtain fluorescent Ti3C2 nanoflakes (0.5–1.5 nm in thickness,
with a lateral size of <9 nm). The Ti3C2 samples exhibited excitation-dependent emission, with an

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Box 2. MXenes: Properties and Main Fields of Application

The structure and physicochemical properties of MXenes have been extensively studied. Recent work has
mainly focused on the mechanical and electronic – metallic and semiconducting – properties of MXenes
[112–114], as well as on their surface chemistry [115], optical [116], and magnetic properties [31]. MXenes
with no terminal surface groups are known to be metallic; however, terminated MXene sheets are narrow
band-gap semiconductors, depending on the location and orientation of the surface groups. Apart from these
aspects, several other outstanding properties make MXenes ideal candidates for applications in various
biotechnological fields. These properties include low cytotoxicity in vitro to nonmalignant cells, some selec-
tivity towards cancerous cells [53], low ecotoxicity [117] and phytotoxicity [118], and efficient antibacterial
properties [102]. Their tunable optical and magnetic properties also make MXenes useful for biosensing and
bioimaging. Their unique potential for use in theranostics, drug delivery, and tissue engineering is expressed
by their efficient NIR absorption and ‘light-to-heat’ transition conversion [119]. This high potential can be
further expanded through surface modifications and the preparation of hybrid multifunctional structures.
The size, stoichiometry, and chemical composition of the surface of MXenes can be optimized by changing
the identity and ratio of their precursor compounds, reaction temperatures and pressures, and the ultrasoni-
cation conditions [51]. The surface of MXenes can be further tailored by using specific biomolecules [120]
and NPs which allow the development of, for example, MRI nanoprobes which can potentially be simulta-
neously used for drug transport and imaging [31].

excitation shift from 340 to 500 nm and a corresponding emission peak shift from 460 to 580 nm [24].
However, fluorescence-based techniques are not suitable for medical diagnosis or in vivo studies
owing to the poor penetration of UV/visible light in tissues. Thus, various other techniques have
been applied which enable the observation of living organisms, including those utilizing X-ray radi-
ation or ultrasound [25].

X-ray computed tomography (CT) is a useful diagnostic tool because of its high resolution, noninva-
siveness, and ability to generate 3D images [26]. The most common CT contrast agents are iodine-
containing compounds, but these have short blood circulation times, high toxicity, or can cause kid-
ney damage [27,28]. A superior approach for CT bioimaging is to use compounds containing more
biocompatible elements. Tantalum-rich Ta4C3 MXenes are excellent candidates for CT imaging
contrast agents in view of their suitable nanoparticle (NP) size, excellent biocompatibility, and eco-
friendly synthesis [29–31].

Another technique using MXenes for tissue visualization is photoacoustic (PA) imaging, which is
based on the conversion of optical energy into acoustic energy. However, the penetration depth
of PA is limited and depends on the laser wavelength [32]. Moreover, it does not employ harmful
X-rays and instead uses nonionizing laser radiation in the visible or IR range [25]. Lin and colleagues
demonstrated the use of Nb2CPVP (polyvinylpyrrolidone) as a contrast agent for PA [33]. In addition,
Ta4C3 has been reported to be suitable for bioimaging tumors using both CT and PA. Lin and co-
workers proposed the use of Ta4C3 nanosheets stabilized via surface modification using soybean
phospholipids (SP) [33]. A crucial parameter that determines the behavior of nanostructures in living
tissues [34] is their colloidal stability, which increases the biocompatibility of materials [33].

Dai and coworkers [35] used a different approach to obtain a MnOx/Ti3C2 composite for imaging
based on PA and magnetic resonance imaging (MRI) techniques. MRI is another powerful
noninvasive technique for imaging tissues in patients [36] and has capabilities similar to CT,
but without the use of harmful X-rays. It is also an alternative for patients who are allergic to CT
contrast agents [37]. Typical MRI contrast agents are based on gadolinium and have been reported
to increase the risk of kidney damage [38]. Thus, the FDA approved a Mn-based substance
(MnCl2$4H2O) as a suitable MRI contrast agent [39]. Therefore, novel biocompatible Mn-containing
MRI contrast agents appear to have potential for use in the clinic. Because nanosized manganese
oxide can be directly grown on the surface of Ti3C2, such composites have been applied in tumor mi-
croenvironments as responsive MRI contrast agents [35]. Attempts to prepare agents for single or
multifunctional imaging techniques were also performed by Liu and coworkers, who developed a

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Figure 1. MXenes as Novel Bioactive Materials and Their Representative Applications in Biophotonics,
Biosensing, Antimicrobial Treatment, Purification of Waste Water, and Nanomedicine – A Scheme.
Exemplary 2D nanoflakes of material discussed in this review are presented in the lower right and left corners. The
middle scanning electron microcopy (SEM) picture shows 3D the book-like nanostructure of MXenes before the
delamination process.

Ta4C3 MXene/superparamagnetic iron oxide (IONP) nanocomposite [31]. CT imaging was possible
because of the presence of tantalum, and the IONP segment allowed the material to be used in
MRI [31]. A different strategy was reported by Zong and colleagues [40], who described the deposi-
tion of GdW10 onto the surface of Ti3C2 nanosheets. Owing to the presence of tungsten and gado-
linium in the functionalized MXene, the fabricated composites could be used for both MRI and CT
imaging [40].

Anticancer Therapy
The properties of MXene also allow their use in bioimaging and anticancer therapies. Cancer is
currently one of the major causes of death worldwide [41]. Traditional cancer therapies, such as
chemotherapy or radiotherapy, suffer from disadvantages, such as low selectivity, which leads to
many side effects or ineffective treatment [42,43]. Therefore, there is a strong need to develop new
cancer treatment methods. It is possible to obtain enhanced selectivity by using light-controlled ther-
apies, including photothermal therapy (PTT), in which photothermal agents are delivered to cancer
tissues which convert laser light energy into heat, killing the tumor cells [44]. To be applied in PTT,
materials should exhibit efficient light-to-heat energy conversion, biocompatibility, and simple sur-
face functionalization. Owing to poor tissue penetration by visible light, it is better to use NIR irradi-
ation which corresponds to so-called ‘tissue optical windows’ or ‘biological windows’ [45]. Many
nanomaterials have been reported to be useful in PTT, for example, Au nanorods [46], copper sulfide
NPs [47], black phosphorus [48], and carbon-based nanomaterials [49]. Recently, MXenes have also
been introduced as novel PTT agents (Table 1). Xuan and coworkers proposed a method to prepare
Ti3C2Tx MXenes with NIR absorption, terminated with an Al oxyanion [50]. In contrast to classical

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 Trends in Biotechnology

Biotechnology (2019), https://doi.org/10.1016/j.tibtech.2019.09.001

Please cite this article in press as: Szuplewska et al., Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in
MXenea Photothermal Extinction Laser power Concentration Laser power Administered Blood Imaging Refs
conversion coefficient density for in vitro (for PTT) density for dose in vivo (for circulation half- technique
efficiency h (%) (l.g1 cm1) in vitro PTT (mg.ml1) in vivo PTT PTT) (mg.kg1) life T1/2 (h)
(W.cm1) (W.cm1)

Ti3C2-PEG No data 29.1 1.0 50 No data No data No data No data [50]

Ti3C2-SP 30.6 25.2 1.0 100 1.5 20 0.76 No data [9]

MnOx/Ti3C2-SP 22.9 5.0 1.0 160 1.5 2.5 No data MRI [35]

Ti3C2 QDs 52.2 52.8 No data No data 0.5 0.5 No data PA, [52]
fluorescence

Ta4C3-SP 44.7 4.06 1.0 100 1.5 20 (intravenous) 1.59 PA, CT [30]
4 (intratumoral)

MnOx/Ta4C3-SP 34.9 8.67 2.0 200 2 20 No data PA, CT, MR [29]

Ta4C3-IONP-SP 32.5 4.0 1.5 200 ppm 1.5 20 0.5 PA, CT, MR [31]

GdW10/Ti3C2 21.9 22.5 1.5 200 ppm 1.5 20 0.83 MR, CT [40]

Nb2C-PVP (laser 36.4 37.6 1.0 100 1.0 20 1.31 PA [33]

808 nm vs laser
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45.7 35.4 1.0 1.0

1064 nm)

Ti3C2-DOX-HA 58.3 28.6 1.5 100 0.8 2 No data Fluorescence [21]

Ti2C-PEG 87.1 7.39 1.5 62.5 No data No data No data No data [53]

Table 1. MXenes and Their Composites for Photothermal Therapy and Their Parameters
a
In each case the cells were cultured in the form of a monolayer and irradiated using a 808 nm laser.
5
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synthetic methods [51], the synthesis resulted in sheets terminated with OH or F which were shown
to be good photothermal agents against murine breast cancer cells [50]. Dai and colleagues [35]
described the preparation of MnOx/Ti3C2 composites for PTT and bioimaging (section on
Bioimaging) which had a lower photothermal conversion efficiency than Ti3C2 nanosheets. However,
after surface modification with SP they effectively killed cancer cells in vitro, and also suppressed
the growth of murine breast tumors in vivo after irradiation with an IR laser [35]. Another line of
research on this subject was performed by Yu and coworkers [52], who presented a simple and
safe fluorine-free method to prepare titanium carbide Ti3C2 QDs for PTT. The fabricated Ti3C2
MXene-based QDs exhibited one of the highest photothermal conversion efficiencies among MXene
materials. In vitro and in vivo tests confirmed their biocompatibility, and the obtained nanosheets
were effective in killing cervical cancer cells after intravenous injection into mice [52] at a lower con-
centration than reported for Ti3C2-SP prepared using a traditional method [9]. Moreover, reduced
laser power density was needed to use Ti3C2 MXenes for tumor ablation compared with previous
studies [9].

Szuplewska and colleagues [53] performed a PTT procedure using a 2D Ti-based MXene with
different stoichiometric amounts of Ti2C. The potential use of the nanostructures generated as pho-
tothermal agents was evaluated against nonmalignant and cancerous cell lines derived from two
different human tissues. This approach allowed the selectivity of MXenes towards malignant cells
to be studied, as well as a comparison of the affinity of nanoflakes for different types of cells. The syn-
thesized Ti2C exhibited excellent performance in NIR-induced killing of cancerous cells. It should be
stressed that the MXenes negligibly affected the viability of normal cells after being exposed to the
nanomaterial at a relatively high concentration (over 35 mg.ml–1). This effect might be attributed to the
tendency of the material to preferentially accumulate in cancerous cells, as was confirmed by
analyzing cellular uptake using scanning electron microcopy (SEM) and confocal microscopy. In addi-
tion, the photothermal conversion efficiency of Ti2C-PEG was superior to other Ti-based nanostruc-
tures [53].

In addition to titanium-containing MXenes, other MXene compounds have been reported to be use-
ful in anticancer therapy. For example, Lin and coworkers evaluated the PTT ability of novel tantalum
carbide (Ta4C3) MXene sheets (Figure 2) [30]. Ta4C3 showed a better photothermal conversion effi-
ciency than was previously reported for Ti3C2 MXene. They also demonstrated good photothermal
stability and, after surface modification with SP, demonstrated good colloidal stability in physiolog-
ical media. Moreover, Ta4C3-SP exhibited a longer blood circulation half-life than Ti3C2-SP, but they
reported a slightly lower accumulation level in tumors because of differences in NP size and the
enhanced permeability and retention (EPR) effect [30]. Another example of using tantalum-based
MXenes was presented by Dai and coworkers [29], who produced MnOx/Ta4C3 composites using
an in situ reaction analogous to that used to prepare Ti3C2 MXene [29]. Tantalum-based composites
exhibited a higher photothermal conversion efficiency than the previously reported MnOx/Ti3C2.
Moreover, the ability to use MnOx/Ta4C3 in various bioimaging techniques is undoubtedly a great
advantage (see Bioimaging and Table 1) [29].

The majority of PTT agents show an absorption peak in the first biological window (NIR-I) [54–57],
including the MXene examples described above [30,31,35,49,52,58]. However, the maximum permis-
sible exposure (MPE), which corresponds to the maximum safe laser power density for human skin
exposure, is higher for NIR-II than for NIR-I. Lin and colleagues [33] described the use of niobium car-
bide (Nb2C) for PTT modality in both biological window regions. To ensure stability and biocompat-
ibility in physiological conditions, the surface of Nb2C sheets was modified with PVP. Nb2C MXenes
exhibited good photothermal conversion efficiencies at both 808 nm and 1064 nm [33].

In addition to efficient light-to-heat conversion, PTT materials should localize at tumor sites. Some
studies have shown that the accumulation level of NPs in tumors is not as high as in other organs
such as liver and spleen [59–61]. Therefore, novel photothermal agents should have sufficient tumor
accumulation to have a therapeutic effect and also good biocompatibility to prevent damage to
healthy tissues without irradiation. The obtained Nb2C-PVP MXenes tended to accumulate in

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Figure 2. Microscopy Image of Cells after Photothermal Therapy (PTT) Using Ta4C3-Soybean Phospholipids
(SP) as a Photothermal Agent.
Green objects are living cells (stained with calcein-AM); red points are dead cells (stained with propidium iodide).
Scale bar, 100 mm. Reprinted, with permission, from [35].

cancerous cells, as confirmed by inductively coupled plasma atomic emission spectroscopy (ICP-
OES) and confocal microscopy (FITC-labeled Nb2C-PVP). The in vivo tumor accumulation of the
MXene was as high as 2.2% of the injected dose, as revealed by ICP-OES and thermogravimetric anal-
ysis, and its blood circulation half-life was 80 minutes. The PTT in both biological window regions was
highly effective [61], and following PTT the applied photothermal agents were easily excreted from
the body. The biodistribution and excretion routes of NPs in an organism depend on many parame-
ters, including their size [49,62], chemical composition [63], surface charge [64], dose [65,66], surface
modification [64], and time [59,67,68]. The biodegradation of Nb2C-PVP has also been addressed by
Lin and colleagues [33]. The authors applied human myeloperoxidase, a naturally occurring enzyme in
humans that is capable of degrading carbon-based substances, to biodegrade Nb2C sheets. Ex vivo
biodegradation was observed after incubating the sheets for 24 h with the enzyme in the presence of
H2O2. The size of the sheets was reduced, their shape was changed, and solution absorbance was
decreased. In addition, biodegradation was also observed during an in vivo experiment, when almost
20% of the introduced Nb2C-PVP was excreted from mice by 48 h post-injection [33].

Recently, PTT was tested in combination with other anticancer therapies, such as traditional chemo-
therapy and photodynamic therapy (PDT) [69]. Some advantages were observed in combined ther-
apies, including synergistic effects, which occur when the simultaneous efficacy of two or more com-
bined therapies is greater than is obtained by separate application of individual treatments [70,71].
This allowed lower drug doses to be used during chemotherapy, as well as reduced concentrations
of photothermal agents and photosensitizers, and lower laser powers for PTT and PDT, which led to
fewer side effects and good treatment results. Many photothermal agents exhibit satisfactory effects
when combined with other antitumor treatment methods, including Au nanorods [72], Cu2xS NPs
[73], and carbon nanospheres [74]. The use of MXenes in combined therapy has also been studied.
Liu and colleagues [21] presented a Ti3C2-based tumor-targeting nanoplatform for synergistic PTT,
PDT, and chemotherapy [21]. Ti3C2 showed an excellent photothermal conversion efficiency, and
the obtained MXene was further loaded with DOX using layer-by-layer adsorption for chemotherapy

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(the DOX loading efficiency was determined spectrophotometrically to be 84%). In addition to pas-
sive tumor accumulation through EPR, the authors achieved active tumor targeting by coating the
MXene with HA, which has an affinity towards cancer cells that overexpress CD44. The nanoplatform
tended to produce high concentrations of reactive oxygen species (ROS) after HA degradation. A
synergistic effect after in vivo PTT using Ti3C2-DOX was observed because DOX alone or Ti3C2-
DOX without laser irradiation led to only partial tumor growth inhibition, and the applied Ti3C2
MXene and DOX doses were low [21].

Different MXene-based materials have been reported to be useful for bioimaging, diagnosis, and
PTT, but some MXenes require low dosages or the application of lasers with high power densities.
In addition, there is a lack of research to determine whether and how MXenes are cleared from the
body, and their possible long-term influence on living organisms. Such studies are necessary, and
they may distinguish different MXenes from each other and assist in the selection of the most appro-
priate material given that all MXenes seem to induce hyperthermia. The mechanism of action of
MXenes and their influence at the single-cell level should also be studied, but only one study has
examined this problem. Jastrze˛bska and coworkers showed that high concentrations of Ti3C2 MXene
tended to generate ROS in skin and lung cells. The observed oxidative stress phenomena was pro-
posed as the main mechanism of action of MXenes [75].

Sensors
The concentrations of many substances are monitored using sensors to ensure human and environ-
mental safety; for example, pesticides in food [76]. The main sensor performance requirements are a
low limit of detection (LOD), high sensitivity, short response time, wide linear range, and good selec-
tivity for a specific analyte or group of analytes. In addition, they should have a low production cost for
ease of commercialization [77]. 2D materials, such as graphene [78] or MoS2 [79], have been described
as biocompatible (bio)sensors for analyte recognition, and a new group of 2D MXene materials has
also recently been studied for this purpose (Table 2).

The properties of MXenes make them interesting candidates for sensing applications. For instance,
zinc ions were reported to selectively quench the luminescence of MQDs, even in the presence of
other metal ions [22], and could therefore be used to construct Zn2+ sensors. Sensors or single-use
tests using MXenes in their sensing layers have also been reported. Liu and coworkers [80] proposed
the use of a mediator-free nitrite biosensor containing hemoglobin (Hb) immobilized on Ti3C2
MXenes as a protein-binding platform. The large surface area of the MXenes ensured that Hb main-
tained its native form after immobilization. Moreover, the direct energy transfer (DET) of Hb was
possible because of the high electronic conductivity of the MXene. DET is difficult to obtain, espe-
cially on a bare electrode, but it is beneficial for mediator-free biosensors. The reduction of nitrite
on the surface of the Nafion/Hb/MXene-Ti3C2/glassy carbon electrode was dependent on the pH
and the bioactivity of Hb, and the optimal sensitivity of the nitrite biosensor was obtained at a pH
of 5.5. The sensor exhibited a low LOD and had a wide dynamic response range, and has been
used to detect the presence of nitrite in environmental water samples [80]. A similar approach was
reported by Wang and colleagues, who developed an H2O2 mediator-free biosensor based on
Ti3C2 MXenes and Hb immobilized on the MXene surface [81]. The selectivity of such sensors is ob-
tained because of the difference in the standard electrochemical potentials of H2O2 [H2O2/H2O (H+)
Eo = 1.74V] and nitrate [NO2/NO3 (H+) Eo = 0.94V] [74,75]. Another example of H2O2 detection us-
ing an MXene-based sensor was presented by Lorencova and coworkers [82]. Both pristine and
oxidized Ti3C2Tx (where T = O, OH, F) delaminated MXenes were deposited on a glassy carbon elec-
trode using a drop-casting method to form MXene aggregates with a size of a few micrometers.
Compared with previously described H2O2 sensors, the MXene-based sensor had a similar or even
better sensitivity, with a comparable LOD [82]. Rakhi and colleagues developed a glucose biosensor
based on an Au/MXene nanocomposite [77]. The proposed tool utilized glucose oxidase (GOx) which
catalyzes the conversion of glucose into gluconolactone and H2O2. The enzyme was deposited onto a
Nafion-solubilized Au/MXene nanocomposite over a glassy carbon electrode (GCE), and the perfor-
mance parameters of the fabricated GOx/Au/MXene/Nafion/GCE sensor were compared with those

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Analyte MXene Detection system Response Linear range Limit of Sensitivity Refs
time detection

Nitrite Ti3C2 Amperometric <3 s 0.5–11800 mM 0.12 mM No data [80]

H2O2 Ti3C2 Voltammetric <3 s 0.1–260 mM 20 nM No data [81]

2 1
H2O2 Pristine and Chronoamperometric 10 s No data 0.7 nM 596 mA.cm .mM [82]
oxidized
Ti3C2Tx
MXene

Glucose Ti3C2Tx Amperometric 10 s 0.1–18 mM 5.9 mM 4.2 mA.M1.cm2 [77]

Volatile organic Ti3C2Tx Resistive No data No data 9.27 ppm No data [83]
compounds

Single nucleotide Ti3C2Tx Electrochemiluminescent No data No data 1 nM No data [84]

8
Tripropylamine Ti3C2Tx Electrochemiluminescent No data 1.0 3 10 to 5 nM No data [84]
1.0 3 103

Dopamine Ti3C2 Conductometric No data 100 nM to 50 mM 100 nM No data [85]

Human bending- Ti3C2 Resistive <10 ms No data 351 Pa Gauge factor
180.1 [86]
release activities

Humidity Ti3C2 Resistive, gravimetric 100 s 0–85% relative 0.8% relative 3% [87]
humidity humidity

Organophosphorus Ti3C2Tx Amperometric No data 1 3 1014 to 0.3 3 1014 M No data [87]

pesticides 1 3 108 M

Table 2. MXene-Based Sensors and Their Parameters

of a GOx/MXene/Nafion/GCE sensor. Dispersion of Au NPs on the surface of MXene nanosheets

improved the electrical conductivity of the proposed system. An Au/MXene composite was charac-
terized by better electrochemical transducer/enzyme immobilization properties than bare MXene.
The nano Au-induced electronic properties in the Au/MXene nanocomposite resulted in faster
charge transport within the GOx/Au/MXene/Nafion/GCE bioelectrodes. In consequence, better
electrocatalytic performance for analyte detection was observed. The presence of Au NPs improved
the electron transfer process between GOx and GCE. Compared with the latter sensor, the Au NP-
containing sensor had a shorter response time, a wider linear range, and a lower LOD. The electrode
was also stable for 2 months and exhibited great repeatability and reproducibility. Moreover, it was
selective for glucose in the presence of other electroactive substances [77]. Some attempts to
develop MXene-based devices capable of detecting biomarkers (e.g., ammonia in lung diseases)
were performed by Lee and colleagues, who described a wearable volatile organic compound sensor
that operated at environmental temperatures [83]. Ti3C2Tx nanosheets were deposited on flexible
polyimide films though a solution casting method, and the MXene film thickness reached 30 nm on
two interdigitated platinum electrodes. Elemental analysis confirmed the presence of oxygen and hy-
droxyl groups on the MXene surface which were beneficial for gas-sensing applications. The sensing
mechanism was based on the adsorption or desorption of sensed gases (by both defects and func-
tional groups) on the nanomaterial surface [83]. A different approach was developed by Fang and co-
workers [84], who developed a tool capable of detecting a single-nucleotide mismatch in human urine
which may serve as an indicator of diseases related to gene mutations. The sensor detected electro-
luminescence (ECL) via the reaction between tris(2,20 -bipyridyl)ruthenium(II), (Ru(bpy)3)2+, immobi-
lized on the surface of the electrode with DNA nucleotides. The sensor was also evaluated as a
solid-state ECL sensor using tripropylamine as a model ECL coreactant, and the sensor exhibited
long-term stability, reproducibility, and a low detection limit [84].

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MXenes have also been reported as useful substances for constructing field-effect transistors (FETs)
to analyze cellular functions. Xu and coworkers developed a Ti3C2-based FET biosensor to detect
dopamine and monitor neural activity [85]. The ultrathin (ca 5 nm) micropatterned MXene layer was
prepared by microcontact printing and was sufficiently transparent to allow microscopic observations
during long-term neural cell cultures. The device consisted of a biosensing compartment and a tran-
sistor structure, and the microinjector dosed femtoliters of samples into the biosensing chamber.
When dopamine molecules reached the MXene surface, they interacted with electrons from the sur-
face MXene groups, leading to enhanced conductance, which was measured by the FET in real-time.
The LOD was very low, and the linear range of the sensor was relatively wide. Moreover, the device
was applied for neuronal cell cultures, where the MXene surface was modified with poly-L-lysine
and laminin to promote cellular adhesion. Calcium monitoring and electrical measurements were
simultaneously performed using the FET sensor [85].

MXenes also exhibit good mechanical stress responses. Ma and coworkers [86] described the prep-
aration of a Ti3C2-based piezoresistive sensor for human bending/release activities such as swallow-
ing, coughing, or joint bending. The sensor was constructed from three layers: a flexible polyimide
film with interdigitated electrodes and an MXene layer that was covered with a flexible polydimethyl-
siloxane film. The authors used this MXene-based sensor to construct electronic skin and other wear-
able devices for real-time monitoring of human parameters in <30 ms [86].

Zhou and colleagues [87] reported the use of a sensor built from MXenes and chitosan to detect mal-
athion and other organophosphorus pesticides (OPs) by using the composite as an immobilization
platform for the enzyme acetylcholinesterase, which was used because it is inhibited in the presence
of OPs. MXenes have advantages in such applications because of their low cytotoxicity, high ’surface-
to-volume’ ratio, and excellent electrical performance [87].

Another potential application of MXenes in sensors was described by Muckley and colleagues [88],
who observed that the spacing between Ti3C2 layers increased after intercalation of K+ and Mg2+
ions, possibly because of water adsorption onto the hydrophilic MXene surfaces. The MXenes
showed both resistive and gravimetric responses for water and humidity in air, but better results
were observed for air relative humidity measurements [88].

Environmental Applications
Heavy metals tend to accumulate in living organisms [89,90], and should therefore be removed from
drinking water. Some theoretical studies on MXene pollutant adsorption properties have been per-
formed and have demonstrated the potential use of MXenes to adsorb harmful substances such as
uranyl [91], ammonia [92], and heavy metals [93,94] (Table 3). Peng and coworkers [95] prepared
Ti3C2(OH/ONa)xF2x MXenes via chemical exfoliation and subsequent alkalization intercalation.
The MXenes generated adsorbed more Pb(II) than other divalent ions such as Ca(II) and Mg(II) in
the same aqueous solution likely because of the presence of the Ti–O bond in the MXenes which
has high affinity for Pb(II). This promoted the formation of a so-called inner-sphere complex [95].
Peng and colleagues published another study on the removal of toxic water pollutants [96]. The au-
thors showed that the redox properties of 2D Ti3C2Tx MXenes provided excellent candidates for one-
step removal of highly toxic chromium(VI) from water. The MXenes were able to facilitate the reduc-
tion of Cr(VI) to less-toxic Cr(III) under acidic conditions. Moreover, the produced Cr(III) ions were ad-
sorbed on the surface of MXenes, which decreased the Cr(VI) concentration in water to a safe level.
The obtained MXenes reduced other oxidants from water, for example, KMnO4, by simply mixing the
oxidant solution with an MXene suspension [96]. Shahzad and colleagues [97] performed a study
aimed at developing a system to remove copper from water using delaminated and multilayered
Ti3C2Tx MXenes owing to their ability to facilitate the adsorption of Cu2+ and subsequently form
Cu2O and CuO on the MXene surface. Delaminated MXenes showed superior copper removal,
and the adsorbents showed an adsorption capacity superior to that of commercially available
activated carbon [97]. Research on a system for water pollutant adsorption was also performed by
Zhang and coworkers [98], who proposed the use of Ti3C2OH0.8F1.2 MXene/magnetic iron oxide

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Adsorbate Adsorbent Capacity Refs

1
Lead (II) Ti3C2(OH/ONa)xF2x 2800 mg.g [95]
1
Chromium (VI) Ti3C2Tx MXene 250 mg.g [96]
1
Copper Ti3C2Tx MXene 78.45 mg.g [97]
1
Phosphate Ti3C2OH0.8F1.2 MXene/Fe2O3/Fe3O4 1.2 mg.g [98]
nanocomposites

Mercury Ti3C2Tx/Fe2O3 nanocomposites 1128.41 mg.g1 [122]

1
Methylene blue Ti3C2Tx MXene 39 mg.g [100]
1
Methylene blue NaOH-Ti3C2Tx MXene 189 mg.g [123]
1
LiOH-Ti3C2Tx MXene 121 mg.g

KOH-Ti3C2Tx MXene 77 mg.g1

Ti3C2Tx MXene 100 mg.g1

Methane Ti3C2 MXene 8.5 cm3.g1 [101]

Ti2C MXene 11.6 cm3.g1

Table 3. MXene-Based Adsorbents and Their Parameters

nanocomposites to remove phosphate ions from water. The adsorbent was fabricated from MXene
layers intercalated with Fe2O3 to increase the sorption capability, and Fe3O4 molecules were distrib-
uted on the MXene surface to enable magnetic separation, which improved the adsorption proper-
ties compared with bare MXenes. Moreover, the obtained system exhibited better sorption capacity

Figure 3. The Chemistry of the Material Surface Determines Nanocrystal Affinity for Biological Systems.
Scanning electron microcopy (SEM) images of exfoliated Ti3AlC2 by fluoride salts (A) LiF with HCl at 50 C for 48 h;
(B,C) NaF and KF with HCl at 40 C for 48 h; (D) NH4F with HCl at 30 C for 24 h. Reprinted, with permission, from
[121].

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Figure 4. Scanning Electron Microcopy (SEM) Images of Ti2C Sheets with Adsorbed Bacteria.
(A) Bacillus sp.; (B) Staphylococcus aureus; (C) Sarcina. The high-magnification insets present in detail the
morphology of the adsorbed cells. Reprinted from [102] under a Creative Commons license.

and selectivity for phosphate in the presence of other anionic compounds, compared with commer-
cially available adsorbents. In addition, the effective regeneration of the nanocomposites using an
alkaline brine solution was also possible [98]. Dyes derived from the textile or food industries have
also been reported to be a target of MXene-based adsorbents because it is relatively expensive to
remove dyes from wastewater [99]. Mashtalir and colleagues [100] studied the properties of Ti3C2Tx
for adsorbing and decomposing organic compounds in aqueous media in the dark or after exposure
to UV light. Because MXenes have a negatively charged surface, only time-dependent removal of
methyl blue from water was observed in the dark because of electrostatic interactions. By contrast,
in the presence of UV light, the concentrations of both methylene blue (MB) and AB80 dyes in
aqueous solutions decreased over short period of time [100], demonstrating that these MXenes
are excellent adsorbents for water purification. Liu and colleagues [101] prepared two types of
MXenes (Ti3C2 and Ti2C) and applied various reagents during synthesis to obtain MXenes with
different gas adsorption properties.

The traditional etching process employs hydrofluoric acid (HF), and results in MXenes terminated
with only OH, F, and O in various proportions. Four types of cations (Li+, Na+, K+, or NH4+) were
chosen to be studied as components of the etchant solution, and the composition of the etching
solution was shown to influence the elemental composition and shape of MXenes, as well as their
methane adsorption capacity and desorption properties (Figure 3). Generally, Ti2C MXenes ex-
hibited better adsorption compared with Ti3C2, which was attributed to their threefold higher sur-
face area. Ti2C MXenes exfoliated with NH4F tended to retain captured methane molecules without
releasing them for long periods of time. By contrast, MXenes prepared using NaF and KF adsorbed
methane molecules under high pressure and released them under low-pressure conditions. This
work increased our understanding of the influence of MXene preparation methods on their adsorp-
tion properties, and also demonstrated the potential use of MXenes as adsorbents in different ap-
plications [101].

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The sorption of chemical compounds using MXenes has also been reported, as has the biological
Outstanding Questions
sorption of bacteria. Jastrze˛bska and colleagues [102] studied the growth of Gram-positive bacteria
Typically, in vitro studies are per-
(Bacillus sp., Staphylococcus aureus, and Sarcina) on the surface of MXenes. The MXenes did not
formed on cell cultures grown in
negatively influence the bacterial cultures and, interestingly, the proliferation of Bacillus sp. was
the form of a monolayer. How do
slightly intensified, and minor apoptosis of bacterial cells was observed (Figure 4). Changes in MXenes influence more advanced
zeta potential were also observed following bacterial adsorption [102]. By contrast, opposite con- 3D biological models such as
clusions were drawn by Rasool and coworkers [103] who tested the growth of Gram-negative spheroids or organoids?
Escherichia coli and Gram-positive Bacillus subtilis bacteria in the presence of both single-layer
So far, only one verified mechanism
and few-layer MXene colloidal solutions. The toxicity to bacteria was concentration-dependent,
is known to underlie MXene in vitro
which was attributed to the production of ROS and cell membrane disruption, and the studied
cytotoxicity: ROS generation lead-
MXenes exhibited better antibacterial properties than graphene oxide [104]. Another study by ing to oxygen stress. Do they have
this group focused on the development of antibacterial membranes for use in wastewater treat- any other effect that influences
ment [105]. The authors attempted to prevent biofilm formation on the surface of separation mem- cell killing?
branes, which leads to their occlusion. To address this issue, micrometer-thick pristine and oxidized
The majority of studies have
Ti3C2Tx-based membranes were deposited on a polyvinylidene fluoride substrate. The antibacterial
focused on MXene action after rela-
properties against Gram-negative E. coli and Gram-positive B. subtilis were confirmed in both pris-
tively short periods of time (24–
tine and oxidized MXene membranes, but the latter showed better inhibition of bacterial growth 48h). Do MXenes differentially in-
[105]. MXene-based membranes have been reported to be useful for desalination of seawater. fluence cellular viability during
Liu and coworkers [106] developed two versions of 60 nm thin Ti3C2Tx membranes: either free- long-term exposure?
standing or deposited on a commercially available membrane support. Because of low membrane
What is the likely metabolic
thickness, a high water flux during water pervaporation was achieved, and the membrane exhibited
pathway of MXenes? Which analyt-
high salt removal (95%) and long-term stability (100 h) [106]. Li and colleagues exploited the ’light-
ical tools are most suitable for
to-heat’ conversion properties (see Anticancer Therapies) of Ti3C2 MXenes to prepare a membrane studying MXene metabolism?
that operated during sun exposure [107].
How can the thermodynamic stabil-
ity of MXenes and the stability of
Concluding Remarks
their aqueous suspensions be
This review has presented a wide range of applications of MXenes, their derivatives, and MXene- improved?
based composites in bioimaging, nanomedicine, and environmental applications. Recent years
Where do MXenes accumulate in
have witnessed a systematic improvement in the optical and electrochemical properties, as well as
organisms after imaging or thera-
the stability, of MXenes and MXene-containing composites. Because of their optical parameters,
peutic procedures, and how they
MXenes can be used for bioimaging, and their outstanding light-to-heat conversion efficiency makes can be removed from the patient’s
them suitable as PTT agents. The chemistry of MXenes makes it possible to develop highly effective body after treatment?
and noninvasive anticancer therapies because of their photodynamic/photothermal/chemothera-
peutic synergistic effects. How can we manipulate the selec-
tivity of MXenes for cancer cells to
make them more efficient drugs or
Beyond their biomedical applications, the electrical conductivity of MXenes makes them suitable can-
drug carriers?
didates for biosensors, and they have also been used as adsorption systems because of their high sta-
bility, hydrophilicity, and large surface area. They have also been proposed as antimicrobial agents How can the sensitivity of MXene-
and biosorbents. This comprehensive review has presented the latest advances, trends, and future based sensors be improved? Which
directions of MXene bioapplications. We emphasize that the use of MXenes in modern biotech- MXene phase or composite will be
best to obtain selectivity for the
nology research is still in its infancy, and scientific protocols require standardization and improve-
target analyte?
ments (see Outstanding Questions).
The antimicrobial properties of
Acknowledgments MXenes are still not well explored,
and published results have led to
This work was supported by funding from the National Science Centre in the framework of research ambiguous conclusions. Will it be
project ’SONATA BIS 7’ (grant UMO-2017/26/E/ST8/01073). possible to standardize research
protocols for studying the influence
of nanomaterials on bacterial
References
growth in the future?
1. Geim, A.K. and Novoselov, K.S. (2007) The rise of 4. Bitounis, D. et al. (2013) Prospects and challenges of
graphene. Nat. Mater. 6, 183–191 graphene in biomedical applications. Adv. Mater.
2. Dean, C.R. et al. (2010) Boron nitride substrates for 25, 2258–2268
high-quality graphene electronics. Nat. 5. Pinto, A.M. et al. (2013) Graphene-
Nanotechnol. 5, 722–726 based materials biocompatibility: a review.
3. Lin, Y.M. et al. (2010) 100-GHz transistors from Colloids Surfaces B Biointerfaces 111,
wafer-scale epitaxial graphene. Science 327, 662 188–202

Trends in Biotechnology, --, Vol. --, No. -- 13

 Please cite this article in press as: Szuplewska et al., Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in
Biotechnology (2019), https://doi.org/10.1016/j.tibtech.2019.09.001
Trends in Biotechnology
6. Zhang, Y. et al. (2012) Graphene: a versatile
nanoplatform for biomedical applications.
Nanoscale 4, 3833
7. Liu, Y. et al. (2012) Biological and chemical sensors
based on graphene materials. Chem. Soc. Rev. 41,
2283–2307
8. Shao, Y. et al. (2010) Graphene based
electrochemical sensors and biosensors: a review.
Electroanalysis 22, 1027–1036
9. Lin, H. et al. (2017) Two-dimensional ultrathin
MXene ceramic nanosheets for photothermal
conversion. Nano Lett 17, 384–391
10. Soleymaniha, M. et al. (2019) Promoting role of
MXene nanosheets in biomedical sciences:
therapeutic and biosensing innovations. Adv.
Healthc. Mater. 8, 1801137
11. Lin, H. et al. (2018) Insights into 2D MXenes
for versatile biomedical applications: current
advances and challenges ahead. Adv. Sci. 5,
1800518
12. Fu, Q. et al. (2018) Photoacoustic imaging: contrast
agents and their biomedical applications. Adv.
Mater. 31, 1805875
13. Wojciechowski, T. et al. (2019) Ti2C MXene
modified with ceramic oxide and noble metal
nanoparticles: synthesis, morphostructural
properties, and high photocatalytic activity. Inorg.
Chem. 58, 7602–7614
14. Guo, Z. et al. (2016) MXene: a promising
photocatalyst for water splitting. J. Mater. Chem. A
4, 11446–11452
15. Kalambate, P.K. et al. (2019) Recent advances in
MXene-based electrochemical sensors and
biosensors. TrAC Trends Anal. Chem. 120,
115643
16. Savchuk, O.A. et al. (2016) Determination of
photothermal conversion efficiency of graphene
and graphene oxide through an integrating sphere
method. Carbon N. Y. 103, 134–141
17. Shi, B. et al. (2018) Hydrogen sulfide-activatable
second near-infrared fluorescent nanoassemblies
for targeted photothermal cancer therapy. Nano
Lett 18, 6411–6416
18. Yong, Y. et al. (2015) Tungsten sulfide quantum dots
as multifunctional nanotheranostics for in vivo dual-
modal image-guided photothermal/radiotherapy
synergistic therapy. ACS Nano 9,
12451–12463
19. Deng, X. and Gu, M. (2003) Penetration depth of
single-, two-, and three-photon fluorescence
microscopic imaging through human cortex
structures: Monte Carlo simulation. Appl. Opt. 42,
3321
20. Mu, X. et al. (2017) Black phosphorus quantum dot
induced oxidative stress and toxicity in living cells
and mice. ACS Appl. Mater. Interfaces 9, 20399–
20409
21. Liu, G. et al. (2017) Surface modified Ti3C2 MXene
nanosheets for tumor targeting photothermal/
photodynamic/chemo synergistic therapy. ACS
Appl. Mater. Interfaces 9, 40077–40086
22. Xue, Q. et al. (2017) Photoluminescent Ti3C2 MXene
quantum dots for multicolor cellular imaging. Adv.
Mater. 29, 1604847
23. Gan, Z. et al. (2016) Mechanism for excitation-
dependent photoluminescence from graphene
quantum dots and other graphene oxide derivates:
consensus, debates and challenges. Nanoscale 8,
7794–7807
24. Wang, Z. et al. (2017) Versatile cutting method for
producing fluorescent ultrasmall MXene sheets.
ACS Nano 11, 11559–11565
25. Xia, J. et al. (2014) Photoacoustic tomography:
principles and advances. Electromagn. waves
(Camb) 147, 1–22
14 Trends in Biotechnology, --, Vol. --, No. --
26. Kamalian, S. et al. (2016) Computed tomography
imaging and angiography – principles. Handb. Clin.
Neurol. 135, 3–20
27. Lusic, H. and Grinstaff, M.W. (2013) X-ray-computed
tomography contrast agents. Chem. Rev. 113,
1641–1666
28. Caro, C. et al. (2017) Highly water-stable rare ternary
Ag–Au–Se nanocomposites as long blood
circulation time X-ray computed tomography
contrast agents. Nanoscale 9, 7242–7251
29. Dai, C. et al. (2017) Two-dimensional tantalum
carbide (MXenes) composite nanosheets for
multiple imaging-guided photothermal tumor
ablation. ACS Nano 11, 12696–12712
30. Lin, H. et al. (2018) Theranostic 2D tantalum carbide
(MXene). Adv. Mater. 30, 1703284
31. Liu, Z. et al. (2018) 2D superparamagnetic tantalum
carbide composite MXenes for efficient breast-
cancer theranostics. Theranostics 8, 1648–1664
32. Beard, P. (2011) Biomedical photoacoustic imaging.
Interface Focus 1, 602–631
33. Lin, H. et al. (2017) A two-dimensional
biodegradable niobium carbide (MXene) for
photothermal tumor eradication in NIR-I and NIR-II
biowindows. J. Am. Chem. Soc. 139, 16235–16247
34. Curtis, C. et al. (2018) Colloidal stability as a
determinant of nanoparticle behavior in the brain.
Colloids Surfaces B Biointerfaces 170, 673–682
35. Dai, C. et al. (2017) Biocompatible 2D titanium
carbide (MXenes) composite nanosheets for pH-
responsive MRI-guided tumor hyperthermia. Chem.
Mater. 29, 8637–8652
36. Liu, Y. (2013) Magnetic resonance imaging. In
Current Laboratory Methods in Neuroscience
Research, H. Xiong and H.E. Gendelman, eds.
(Springer), pp. 249–270
37. Sasaguri, K. and Takahashi, N. (2018) CT and MR
imaging for solid renal mass characterization. Eur. J.
Radiol. 99, 40–54
38. Viswanathan, S. et al. (2010) Alternatives to
gadolinium-based metal chelates for magnetic
resonance imaging. Chem. Rev. 110, 2960–3018
39. Small, W.C. et al. (1999) A multisite phase III study of
the safety and efficacy of a new manganese
chloride-based gastrointestinal contrast agent for
MRI of the abdomen and pelvis. J. Magn. Reson.
Imaging 10, 15–24
40. Zong, L. et al. (2018) A polyoxometalate-
functionalized two-dimensional titanium carbide
composite MXene for effective cancer theranostics.
Nano Res 11, 4149
41. Siegel, R.L. et al. (2017) Cancer statistics, 2017. CA.
Cancer J. Clin. 67, 7–30
42. Lorusso, D. et al. (2017) Patients’ perception of
chemotherapy side effects: expectations, doctor–
patient communication and impact on quality of
life – an Italian survey. Eur. J. Cancer Care 26,
e12618
43. Tabish, T.A. et al. (2018) Developing the next
generation of graphene-based platforms for cancer
therapeutics: the potential role of reactive oxygen
species. Redox Biol 15, 34–40
44. Riley, R.S. and Day, E.S. (2017) Gold nanoparticle-
mediated photothermal therapy: applications and
opportunities for multimodal cancer treatment.
Wiley Interdiscip. Rev. Nanomedicine
Nanobiotechnology 9, e1449
45. Martinic, I. et al. (2017) Near-infrared emitting
probes for biological imaging: organic
fluorophores, quantum dots, fluorescent proteins,
lanthanide(III) complexes and nanomaterials.
J. Lumin. 189, 19–43
46. Rao, L. et al. (2018) Platelet-facilitated photothermal
therapy of head and neck squamous cell carcinoma.
Angew. Chemie Int. Ed. 57, 986–991
Please cite this article in press as: Szuplewska et al., Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in
Biotechnology (2019), https://doi.org/10.1016/j.tibtech.2019.09.001
Trends in Biotechnology
47. Li, L. et al. (2017) CuS nanoagents for photodynamic
and photothermal therapies: phenomena and
possible mechanisms. Photodiagnosis Photodyn.
Ther. 19, 5–14
48. Shao, J. et al. (2016) Biodegradable black
phosphorus-based nanospheres for in vivo
photothermal cancer therapy. Nat. Commun. 7,
12967
49. Liu, J. et al. (2017) Comparison of nanomedicine-
based chemotherapy, photodynamic therapy and
photothermal therapy using reduced graphene
oxide for the model system. Biomater. Sci. 5,
331–340
50. Xuan, J. et al. (2016) Organic-base-driven
intercalation and delamination for the production of
functionalized titanium carbide nanosheets with
superior photothermal therapeutic performance.
Angew. Chemie - Int. Ed. 55, 14569–14574
51. Naguib, M. et al. (2012) Two-dimensional transition
metal carbides. ACS Nano 6, 1322–1331
52. Yu, X. et al. (2017) Fluorine-free preparation of
titanium carbide MXene quantum dots with high
near-infrared photothermal performances for
cancer therapy. Nanoscale 9, 17859–17864
53. Szuplewska, A. et al. (2019) 2D Ti2C (MXene) as a
novel highly efficient and selective agent for
photothermal therapy. Mater. Sci. Eng. C 98,
874–886
54. Wang, K. et al. (2018) PEGylated chitosan
nanoparticles with embedded bismuth sulfide for
dual-wavelength fluorescent imaging and
photothermal therapy. Carbohydr. Polym. 184,
445–452
55. Bharathiraja, S. et al. (2018) Multimodal tumor-
homing chitosan oligosaccharide-coated
biocompatible palladium nanoparticles for photo-
based imaging and therapy. Sci. Rep. 8, 500
56. Dong, L. et al. (2018) Multifunctional Cu–Ag2S
nanoparticles with high photothermal conversion
efficiency for photoacoustic imaging-guided
photothermal therapy in vivo. Nanoscale 10,
825–831
57. Liu, J. et al. (2018) Tumor acidity activating
multifunctional nanoplatform for NIR-mediated
multiple enhanced photodynamic and
photothermal tumor therapy. Biomaterials 157,
107–124
58. Hou, L. et al. (2017) In vitro and in vivo comparative
study of the phototherapy anticancer activity of
hyaluronic acid-modified single-walled carbon
nanotubes, graphene oxide, and fullerene.
J. Nanoparticle Res. 19, 286
59. Frellsen, A.F. et al. (2016) Mouse positron
emission tomography study of the biodistribution
of gold nanoparticles with different surface coatings
using embedded copper-64. ACS Nano 10, 9887–
9898
60. Wang, J. et al. (2015) Size- and surface chemistry-
dependent pharmacokinetics and tumor
accumulation of engineered gold nanoparticles
after intravenous administration. Metallomics 7,
516–524
61. Zhou, B. et al. (2016) PEGylated polyethylenimine-
entrapped gold nanoparticles modified with folic
acid for targeted tumor CT imaging. Colloids Surf.
B. Biointerfaces 140, 489–496
62. Lopez-Chaves, C. et al. (2018) Gold nanoparticles:
distribution, bioaccumulation and toxicity. In vitro
and in vivo studies. Nanomedicine
Nanotechnology, Biol. Med. 14, 1–12
63. Yang, L. et al. (2017) Comparisons of the
biodistribution and toxicological examinations
after repeated intravenous administration of
silver and gold nanoparticles in mice. Sci. Rep. 7,
3303
64. Xiao, K. et al. (2015) Role of surface charge in
determining the biological effects of CdSe/ZnS
quantum dots. Int. J. Nanomedicine 10, 7073
65. Zarska, M. et al. (2018) Biological safety and tissue
distribution of (16-mercaptohexadecyl)
trimethylammonium bromide-modified cationic
gold nanorods. Biomaterials 154, 275–290
66. Shahbazi, R. et al. (2017) Functionalized gold
nanoparticles manifested as potent carriers for
nucleolar targeting. Nanotechnology 28, 025103
67. Poon, W. et al. (2015) Targeting B16 tumors in vivo
with peptide-conjugated gold nanoparticles.
Nanotechnology 26, 285101
68. Koyama, Y. et al. (2015) Biodistribution of gold
nanoparticles in mice and investigation of their
possible translocation by nerve uptake around the
alveolus. J. Toxicol. Sci. 40, 243–249
69. Wan, G. et al. (2018) Nanoscaled red blood cells
facilitate breast cancer treatment by combining
photothermal/photodynamic therapy and
chemotherapy. Biomaterials 155, 25–40
70. Sheng, D. et al. (2018) Perfluorooctyl bromide and
indocyanine green co-loaded nanoliposomes for
enhanced multimodal imaging-guided
phototherapy. Biomaterials 165, 1–13
71. Shu, Y. et al. (2018) Thermo/pH dual-stimuli-
responsive drug delivery for chemo-/photothermal
therapy monitored by cell imaging. Talanta 181,
278–285
72. Wang, J. et al. (2018) Metabolomics assisted
metabolic network modeling and network wide
analysis of metabolites in microbiology. Crit. Rev.
Biotechnol. 38, 1106–1120
73. Feng, Q. et al. (2017) An intelligent NIR-responsive
chelate copper-based anticancer nanoplatform for
synergistic tumor targeted chemo-phototherapy.
Nanoscale 9, 15685–15695
74. Wang, X. et al. (2018) Synergistic chemo-
photothermal therapy of tumor by hollow carbon
nanospheres. Biochem. Biophys. Res. Commun.
495, 867–872
75. Jastrze˛bska, A.M. et al. (2017) In vitro studies on
cytotoxicity of delaminated Ti3C2 MXene. J. Hazard.
Mater. 339, 1–8
76. Moon, J.-M. et al. (2018) Conducting polymer-
based electrochemical biosensors for
neurotransmitters: a review. Biosens. Bioelectron.
102, 540–552
77. Rakhi, R.B. et al. (2016) Novel amperometric glucose
biosensor based on MXene nanocomposite. Sci
Rep 6, 36422
78. Lawal, A.T. (2018) Progress in utilisation of graphene
for electrochemical biosensors. Biosens.
Bioelectron. 106, 149–178
79. Sinha, A. et al. (2018) MoS2 nanostructures for
electrochemical sensing of multidisciplinary targets:
a review. TrAC Trends Anal. Chem. 102, 75–90
80. Liu, H. et al. (2015) A novel nitrite biosensor based
on the direct electrochemistry of hemoglobin
immobilized on MXene-Ti3C2. Sensors Actuators B
Chem 218, 60–66
81. Wang, F. et al. (2014) An organ-like titanium carbide
material (MXene) with multilayer structure
encapsulating hemoglobin for a mediator-free
biosensor. J. Electrochem. Soc. 162, B16–B21
82. Lorencova, L. et al. (2017) Electrochemical
performance of Ti3C2Tx MXene in aqueous media:
towards ultrasensitive H2O2 sensing. Electrochim.
Acta 235, 471–479
83. Lee, E. et al. (2017) Room temperature gas sensing
of two-dimensional titanium carbide (MXene). ACS
Appl. Mater. Interfaces 9, 37184–37190
84. Fang, Y. et al. (2018) Two-dimensional titanium
carbide (MXene)-based solid-state
electrochemiluminescent sensor for label-free
Trends in Biotechnology, --, Vol. --, No. -- 15
 Please cite this article in press as: Szuplewska et al., Future Applications of MXenes in Biotechnology, Nanomedicine, and Sensors, Trends in
Biotechnology (2019), https://doi.org/10.1016/j.tibtech.2019.09.001
Trends in Biotechnology
single-nucleotide mismatch discrimination in
human urine. Sensors Actuators B Chem 263,
400–407
85. Xu, B. et al. (2016) Ultrathin MXene-micropattern-
based field-effect transistor for probing neural
activity. Adv. Mater. 28, 3333–3339
86. Ma, Y. et al. (2017) A highly flexible and sensitive
piezoresistive sensor based on MXene with greatly
changed interlayer distances. Nat. Commun. 8,
1207
87. Zhou, L. et al. (2017) Acetylcholinesterase/chitosan-
transition metal carbides nanocomposites-based
biosensor for the organophosphate pesticides
detection. Biochem. Eng. J. 128, 243–249
88. Muckley, E.S. et al. (2017) Multimodality of
structural, electrical, and gravimetric responses of
intercalated MXenes to water. ACS Nano 11,
11118–11126
89. Guinot, D. et al. (2012) Long-term effect of
temperature on bioaccumulation of dietary metals
and metallothionein induction in Sparus aurata.
Chemosphere 87, 1215–1221
90. Ahmed, N. and Oh, S.E. (2018) Toxicity assessment
of selected heavy metals in water using a seven-
chambered sulfur-oxidizing bacterial (SOB)
bioassay reactor. Sensors Actuators, B Chem. 258,
1008–1014
91. Zhang, Y.-J. et al. (2017) Theoretical insights into the
uranyl adsorption behavior on vanadium carbide
MXene. Appl. Surf. Sci. 426, 572–578
92. Yu, X. et al. (2015) Monolayer Ti2CO2: a promising
candidate for NH3 sensor or capturer with high
sensitivity and selectivity. ACS Appl. Mater.
Interfaces 7, 13707–13713
93. Guo, X. et al. (2016) High adsorption capacity of
heavy metals on two-dimensional MXenes: an ab
initio study with molecular dynamics simulation.
Phys. Chem. Chem. Phys. 18, 228–233
94. Guo, J. et al. (2015) Heavy-metal adsorption
behavior of two-dimensional alkalization-
intercalated MXene by first-principles calculations.
J. Phys. Chem. C 119, 20923–20930
95. Peng, Q. et al. (2014) Unique lead adsorption
behavior of activated hydroxyl group in two-
dimensional titanium carbide. J. Am. Chem. Soc.
136, 4113–4116
96. Ying, Y. et al. (2015) Two-dimensional titanium
carbide for efficiently reductive removal of highly
toxic chromium(VI) from water. ACS Appl. Mater.
Interfaces 7, 1795–1803
97. Shahzad, A. et al. (2017) Two-dimensional Ti3C2Tx
MXene nanosheets for efficient copper removal
from water. ACS Sustain. Chem. Eng. 5, 11481–
11488
98. Zhang, Q. et al. (2016) Efficient phosphate
sequestration for water purification by unique
sandwich-like MXene/magnetic iron oxide
nanocomposites. Nanoscale 8, 7085–7093
99. Wong, S. et al. (2018) Recent advances in
applications of activated carbon from biowaste for
wastewater treatment: a short review. J. Clean.
Prod. 175, 361–375
100. Mashtalir, O. et al. (2014) Dye adsorption and
decomposition on two-dimensional titanium
carbide in aqueous media. J. Mater. Chem. A 2,
14334–14338
101. Liu, F. et al. (2017) Preparation of Ti3C2 and Ti2C
MXenes by fluoride salts etching and methane
adsorptive properties. Appl. Surf. Sci. 416, 781–789
102. Jastrze˛bska, A. et al. (2017) Biological activity and
bio-sorption properties of the Ti2C studied by
means of zeta potential and SEM. Int. J.
Electrochem. Sci 12, 2159–2172
16 Trends in Biotechnology, --, Vol. --, No. --
103. Rasool, K. et al. (2016) Antibacterial activity of
Ti3C2Tx MXene. ACS Nano 10, 3674–3684
104. Xiao, F. et al. (2009) Ultrasonic electrodeposition of
goldplatinum alloy nanoparticles on ionic
liquidchitosan composite film and their
application in fabricating nonenzyme hydrogen
peroxide sensors. J. Phys. Chem. C 113, 849–855
105. Rasool, K. et al. (2017) Efficient antibacterial
membrane based on two-dimensional Ti3C2Tx
(MXene) nanosheets. Sci. Rep. 7, 1598
106. Liu, G. et al. (2018) Ultrathin two-dimensional
MXene membrane for pervaporation desalination.
J. Memb. Sci. 548, 548–558
107. Li, R. et al. (2017) MXene Ti3C2: an effective 2D light-
to-heat conversion material. ACS Nano 11 (4), 3752–
3759
108. Naguib, M. et al. (2011) Two-dimensional
nanocrystals produced by exfoliation of Ti3AlC2.
Adv. Mater. 23, 4248–4253
109. Barsoum, M.W. (2000) The MN+1AXN phases: a new
class of solids: thermodynamically stable
nanolaminates. Prog. Solid State Chem. 28, 201–281
110. Wang, H. et al. (2018) Clay-inspired MXene-based
electrochemical devices and photo-electrocatalyst:
state-of-the-art progresses and challenges. Adv.
Mater. 30, 1704561
111. Naguib, M. et al. (2014) 25th anniversary article:
MXenes: a new family of two-dimensional materials.
Adv. Mater. 26, 992–1005
112. Bonaccorso, F. et al. (2015) Graphene, related two-
dimensional crystals, and hybrid systems for energy
conversion and storage. Science 347, 1246501–
1246501
113. Liang, X. et al. (2017) Interwoven MXene nanosheet/
carbon-nanotube composites as Li-S cathode hosts.
Adv. Mater. 29, 1603040
114. Zha, X.-H. et al. (2016) Intrinsic structural, electrical,
thermal, and mechanical properties of the
promising conductor Mo2C MXene. J. Phys. Chem.
C 120, 15082–15088
115. Wang, H. et al. (2018) Chemically functionalized
two-dimensional titanium carbide MXene by in situ
grafting-intercalating with diazonium ions to
enhance supercapacitive performance. J. Phys.
Chem. Solids 115, 172–179
116. Berdiyorov, G.R. (2016) Optical properties of
functionalized Ti3C2T2 (T=F, O, OH) MXene: first-
principles calculations. AIP Adv 6, 055105
117. Nasrallah, G.K. et al. (2018) Ecotoxicological
assessment of Ti3C2Tx (MXene) using a zebrafish
embryo model. Environ. Sci. Nano 5, 1002–1011
118. Rozmysłowska-Wojciechowska, A. et al. (2019)
Influence of modification of Ti3C2 MXene with
ceramic oxide and noble metal nanoparticles on its
antimicrobial properties and ecotoxicity towards
selected algae and higher plants. RSC Adv 9, 4092–
4105
119. Li, R. et al. (2017) MXene Ti3C2: an effective 2D light-
to-heat conversion material. ACS Nano 11, 3752–
3759
120. Rozmysłowska-Wojciechowska, A. et al. (2019)
Surface interactions between 2D Ti3C2/Ti2C
MXenes and lysozyme. Appl. Surf. Sci. 473, 409–418
121. Fu, Y. et al. (2018) Graphene blended with SnO2 and
Pd–Pt nanocages for sensitive non-enzymatic
electrochemical detection of H2O2 released from
living cells. Anal. Chim. Acta 1014, 10–18
122. Shahzad, A. et al. (2018) Mercuric ion capturing by
recoverable titanium carbide magnetic
nanocomposite. J. Hazard. Mater. 344, 811–818
123. Wei, Z. et al. (2018) Alkali treated Ti3C2Tx MXenes
and their dye adsorption performance. Mater.
Chem. Phys. 206, 270–276