Nanotechnology for Environmental Engineering (2021) 6:25

https://doi.org/10.1007/s41204-021-00115-2

CRITICAL REVIEWS

Application of strontium‑based nanoparticles in medicine

and environmental sciences
Sumit Mukherjee1 · Monalisa Mishra1

Received: 2 January 2021 / Accepted: 20 March 2021 / Published online: 24 April 2021
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021

Abstract
The application of nanoparticles is continuously increasing in numerous fields including, medicine and biology, drug delivery,
electronic devices, biosensors, catalysts, and agricultural as well as industrial science. Among the nanoparticles, metallic
nanoparticles have gained significant interest in the past few years due to their unique physical and chemical characters.
Strontium belongs to Group II metallic elements of the periodic table, the same group as calcium and magnesium. Conven-
tionally, strontium is used in bone regeneration, growth stimulant, and ability to stimulate calcium signaling. Henceforth,
strontium-based nanoparticles have gained interest in the field of medicine and dentistry due to their similar property with
calcium. Besides that, strontium-conjugated nanomaterials exhibit the antimicrobial ability and are efficient in the removal
of toxic contaminants from industrial wastewater. Strontium nanoparticles are used in targeted drug delivery and can elicit a
prolonged immune response, thus can act as a good immunotherapeutic agent. The applications of strontium nanoparticles
have also been found in diabetic patients, where they can control the insulin release and thus regulate the pathophysiology
of diabetes. Strontium nanoparticles are also used in wastewater treatment, agriculture, and as gas sensors to sense several
toxic gases. The wide application of strontium nanoparticles in several filed of medicine and environmental sciences is
summarized in this review.

Keywords Strontium-based nanoparticles · Metallic nanoparticles · Nanoparticles · Food · Agriculture

Introduction characteristics appear as a result of their size and shape and

Nanotechnology is widely used in several branches of sci-
ence to improve the quality of life. It is widely used in agri-
culture to enhance the efficacy of fertilizers and to control the
pest with minimal dose [1]. Novel functional materials are
designed to improve safety in the food material [2]. Hence-
forth, surface functionalization is made to target several
drugs in a non-toxic manner [3]. Nanotechnology designs
different types of materials, often known as nanomaterials
of various size and shapes. Among them, nanoparticles are
a vast class of materials having a particle size ranging from
1 to 1000 nm [4, 5]. Nanoparticles gained significant interest
due to its exceptional physical and chemical characteristics.
It includes large surface to area volume ratio, increased sur-
face functionality, bioactivity and biocompatibility. These
* Monalisa Mishra
mishramo@nitrkl.ac.in
1
Neural Developmental Biology Lab, Department of Life
Science, NIT Rourkela, Rourkela, Odisha 769008, India
are often absent from the bulk materials from which the
nanoparticles are produced [6]. Nanoparticles include sev-
eral classes such as ceramic, polymeric as well as metallic
[7]. Among all, metallic nanoparticles have gained special
attention in the area of nanotechnology (Fig. 1) [8]. The
mode of synthesis allows us to achieve the desired character-
istic associated with the metallic nanoparticles [9]. Metallic
nanoparticles are synthesized from various metals, and the
most commonly used metallic nanoparticles include gold,
iron, silver, cerium, titanium, and zinc. Its compound forms
such as sulfides, oxides, fluorides, hydroxides, and chlorides
forms are also available [10, 11]. Strontium belongs to a
trace metal having similar properties as calcium and mag-
nesium, which have important roles in the human body. Due
to its properties, strontium is used as an important element
in bone and tissue engineering and dentistry. Formulation
of strontium and strontium-conjugated nanoparticles have
gained interest in the past few years having well-known
applications in various fields such as, efficient drug deliv-
ery, bioimaging, cancer therapy, bone engineering, as well

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Fig. 1  Application of Strontium nanoparticles
as environmental management, including wastewater man-
agement, toxic gas sensing properties. The current review
summarizes Strontium (Sr) as a potent nanoparticle for the
application in several branches of science.
Strontium as a non‑toxic metal for biological
application
Sr was first discovered in a mine in 1790 and isolated in
1808. It is a soft silvery-white, non-hazardous alkaline earth
metal bearing an atomic number of 38. In oxidized form,
it appears yellowish. Only 0.02–0.03% Sr is available in
the earth’s crust [12, 13]. It occurs naturally as carbonate
­(SrCO3) and sulfates. Sr acts as a growth stimulant in the
chlorella plant and can replace Calcium (Ca) [13]. In ani-
mals, Sr is not an essential element but can prevent caries
in rats when administered in moderate amounts. Sr ranelate
increases bone Ca and reduces fracture percentage in osteo-
porotic patients [14, 15]. Sr is the only trace metal correlated
with bone compression. The transport of Sr ions is mediated
by the same carriers as used for Ca in the central and renal
tubular cells; thus, significant correlation has been observed
between the absorption of Sr and Ca. Therefore, the adminis-
tration of stable Sr has been considered as a suitable practice
for assessing Ca absorption and excretion [16]. However,
a high intravenous dose of Sr resulted from hypocalcemia
due to renal secretion of Ca [17, 18]. Strontium chromate
is known to have carcinogenic and genotoxic effects [19].
The human body differentiates the use between Ca and Sr
based on body functions, for example, mammary secretions,
renal absorption, and gastrointestinal absorption. Sr in cells
and organs mimic the actions of Ca, although the stimulated
response is comparatively weaker [20]. Sr ions were effec-
tive in insulin-mediated glucose cell uptake when there was
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Nanotechnology for Environmental Engineering (2021) 6:25
a Ca and Mg ions deprivation to a certain extent [21]. Sr
can form divalent cations in biological fluids and has pro-
tein binding capacity in plasma or serum, similar to calcium
[22]. Due to its similarities with calcium, Sr is incorporated
in bone repair as ­Sr2+ (ions) and can stay in the body for a
long time. The response of signaling principle and metabolic
pathways for calcium follows Sr albeit the effects are weaker
but have almost similar protein binding capacity. Sr has role
in the development of bone formation. It also inhibits the
bone degradation. During bone formation process, it helps
to enhance the osteoclast activities; however, during degra-
dation it inhibits the osteoclast activities [23]. Sr turns on
the signaling pathways associated with calcium-regulated
bone metabolism by acting on the calcium-sensing receptor
(CaSR) of bone-forming cells (Fig. 3). Sr can decrease the
inhibitors of the Wnt pathway and an increase in β-catenin
expression making an increase in transcription of osteogenic
factors and prostaglandin expression [24, 25]. Sr can replace
Ca during blood clotting and muscle contraction [23]. Sr-
coated halloysite nanotubes (SrHNTs) in bone structure
resulted in the strengthening of the bone and induces bone
formation by osteoblasts. It reduces bone reabsorption, pos-
sesses anti-bacterial activity, and drug loading capacity [26].
Strontium as a metallic nanoparticle
for the modern era
Strontium nanoparticles (SrNPs) are used in drug delivery,
bioimaging, therapy of cancer, and chemosensor. The pre-
cipitation and encapsulation of SrNPs were done within
carboxymethyl cellulose (CMC). Carboxymethyl cellulose
(CMC) is a biocompatible and biodegradable polymeric
material having wide industrial applications, and it is used
as a biological stabilizer to encapsulate SrNPs to develop an
efficient optical nanostructure which can be used in in vivo
imaging. This strontium-suspended vesicle is used in bio-
medical imaging, drug delivery, therapeutics for cancer, and
chemosensing (Fig. 2) [27].
One of the methods to improve the properties of bio-
materials involves the addition of trace quantities of metal
elements within it. These elements play significant roles in
enhancing the biological response, increased mechanical
properties to provide more tenacity and durability, improved
drug release and control of the degradation rate of the mate-
rials [26]. Information about Sr has gained significant inter-
est to be used as an additional element. SrNPs are used for
the significant improvement of the biological and mechani-
cal properties of many polymers and metal alloys [28, 29],
which ultimately led to better and enhanced opportunities
to be used in developing materials in several fields [30, 31].
SrNPs are used in dental implants and orthopedic coat-
ings to promote the bone healing process [26] by inducing
Nanotechnology for Environmental Engineering (2021) 6:25
Fig. 2  Application of Strontium nanoparticles in various fields
osteogenic and osteoinductive properties [32]. It further
enhances the biological response, increases mechanical
properties, drug release, and control of the degradation rate
of biomaterials [26]. The signaling of vascular endothelial
growth factor (VEGF) is essential for stem cell commitment.
Fig. 3  Mechanism of bone for-
mation by Strontium ranelate
Page 3 of 15 25
Sr triggered the secretion of these growth factors associ-
ated with RhoA/Rac1 activation and thereby repressing
adipogenesis and activating osteoblastogenesis in gravity-
induced alteration of cell commitment [33, 34]. Sr-treated
mesenchymal stem cells (MSCs) can increase the phospho-
rylation of mitrogen-activated protein kinase (MAPK). The
extracellular-signal regulated kinases (ERK) and p38 along
with osteogenic differentiation [35]. Strontium ranelate in
lower doses can enhance human adipose-derived stem cells
(hASC) osteogenic differentiation but higher doses can cause
hASC apoptosis by activating ERK signaling pathway [12].
This information lays a strong foundation for Sr-containing
scaffolds for use in bone engineering. Sr-doped magnetic
graphene nanocomposite (SrFeGO NC) was developed as an
active catalyst to synthesize β-enamino ketones from acety-
lacetone and anilines in a solvent-free system [36] (Fig. 3).
Application of strontium nanoparticles
in medical science
Bone regeneration
Sr is the most important cations in bones, which stimulate
the growth of the osteoblast cells and prevent reabsorption
of bone and thus may confront osteoporosis [37–39]. It can
enhance osteoblastic gene expression and the functionality
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25 Page 4 of 15
of alkaline phosphatase (ALP) of the mesenchymal stem
cells (MSCs) and prevent the delineation of osteoclasts. S ­ r2+
incorporated calcium phosphate scaffolds have enhanced
the proliferative and differentiating ability of osteoblastic
ROS17/2.8 cells [39]. ­Sr2+-incorporated mesoporous silica
particles (SrMSPs) of sub-micron size were found to exert
an inductive effect on osteoblast proliferation and differen-
tiation [40]. Besides that, the enhanced proliferative prop-
erty along with ALP action of osteoblast cells has also been
reported for bioactive glasses substituted with Sr [41, 42].
Strontium ­(Sr2+) and iron ­(Fe3+) were co-substituted in a
hydroxyapatite lattice in place of C ­ a2+ ions [43]. ­Sr2+ and
3+
­Fe co-substituted HAp multifunctional bioactive elements
may act as a possible candidate to treat osteoporosis and
bone cancer and improve bone strength [44, 45]. Pristine
HAp also exhibits excellent bioactive features intrinsically;
thus, the inclusion of foreign ions such as Sr and Fe could
produce more soluble compounds with increased bioactiv-
ity. Besides that, the release of S­ r2+/Fe3+ ions can help the
2+
release of C ­ a ions and thus can potentially activate the
calcium ion channels which regulate numerous cellular
activities [46, 47].
Bone filling biomaterials are used for bone tissue graft.
They are comprised of organic and inorganic components
which can mimic the bone extracellular matrix. Thus, it can
have higher bone regeneration potential. Hydroxyapatite is a
frequently used for filling material because of its similarities
with the component of the bone matrix [48]. They can essen-
tially induce the growth of osteoblasts because of their effec-
tive ability to reconstruct the bone defect. Sr-doped HAp/silk
fibroin (SrHAp/SF) biocomposite nanospheres were used as
a bone-defect filling material with osteoinductive properties.
The composite nanospheres contain a high Sr percentage can
survive in mesenchymal stem cells (MSCs). Furthermore,
they exhibited improved differentiation potential of osteo-
blasts compared to HAp/SF nanospheres [48].
Bioactive glasses (BGs) gained vast usage in the augmen-
tation of bone tissue along with bone reconstruction. Besides
that, BGs-coated implants can attach firmly to the surround-
ing living tissues of the host [49–51]. Sr ion is often used to
increase BG’s bioactivity and induce bone formation [52,
53]. A study [41] investigated the potential of Sr inclusive
bioactive glasses, where calcium ions were substituted by Sr
ions and the constructive effects on bone regeneration were
established. Later, a separate study [54] showed osteogenic
differentiation in a medium with BG particles inclusive of
strontium. Porous nanocomposite scaffolds of polycaprolac-
tone (PCL) and various percentages of 45S bioactive glass
nanoparticles comprising Sr were developed for bone tissue
engineering [55].
By using a co-electrospinning technique, compos-
ite nanofibrous scaffolds were prepared from Sr carbon-
ate nanoparticles ­(nSrCO3) and PCL to induce stem cell
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Nanotechnology for Environmental Engineering (2021) 6:25
osteogenesis. Persistent discharge of the Sr ions by the
inclusion of ­SrCO3 nanoparticles can additionally exert
osteogenicity of PCL scaffolds. This nanocomposite further
showed increased expression of known stem cell genes that
supports osteogenesis [56]. SrNPs have been combined with
support surfaces such as polymers, ceramics, clay nanoparti-
cles. SrNPs deposited on the halloysite outer surface shown
enhanced microbial activity. Hydroxy apatite (HAp), and
bioactive glass are low biodegradable, and their mechani-
cal qualities make them impractical candidates for structural
modification. HAp incorporated SrNPs can improve tensile
properties and angiogenic effects. Sr coating on halloysite
nanotubes (HNTs) was beneficial for cell proliferation in
preosteoblast cells, drug release, and inherent antibacterial
properties. SrHNT acts as a good carrier to release gen-
tamicin and methotrexate [26].
Nanoporous silica nanoparticles (NSNPs) were incorpo-
rated with Sr to check the drug delivery behavior. Sr-mod-
ified NSNPs (SrO-silica NPs) can enhance drug loading
capacity and slower release of the loaded drug compared
to normal SNPs. These SrO-silica NPs possess excellent
potentiality to be used in the regeneration of bone tissue via
a sustained discharge in the targeted region. The controlled
release of this NP is helpful in bone tissue regeneration as it
enhances the bioavailability of the drug at a precise rate and
for a more exact period in the destined location. SrO-silica
NPs could be more effectively loaded with an antibiotic
drug, amoxicillin, containing –COOH groups, which can
be used in local delivery to prevent post-surgical bacterial
growth [57].
Postmenopausal osteoporosis has been reported as a prob-
able risk factor for impaired healing of fractures, indicated
by disturbed callus formation and delayed fracture union.
Estrogen is a key hormone involved in the maintenance of
bone mass, with estrogen deficiency a major cause of post-
menopausal osteoporosis due to abnormal bone remodeling
and higher bone resorptive activity [58]. Estrogen deficiency
can also lead to delayed fracture healing and callus forma-
tion. Therefore, in fracture patients having postmenopausal
osteoporosis, resulting in impaired fracture healing may
cause significant morbidity and harm life quality, leading to
a greater economic burden on patients.
Clinical and experimental studies suggest that strontium
ranelate (SR) can improve abnormal bone turnover as indi-
cated by changes in the levels of circulating bone markers
and reduced fracture incidence following treatment [59]. In
a normal rat model, SR administration increased the bone
volume and microarchitecture compared to untreated rats.
Furthermore, several case reports have shown that SR can
promote both bone formation and inhibit bone resorption.
Additionally, it can promote fracture healing by increas-
ing osteogenesis and bone formation in the fracture site,
thereby improving the microstructure of trabecular bone
Nanotechnology for Environmental Engineering (2021) 6:25
and enhancing the biomechanical properties of the callus
[60, 61].
SrNPs in dentistry
Sr can increase bone strength as well as prevent dental car-
ies [62]. HAp considered as the principal mineral compo-
nent of the tooth, and the artificially synthesized HAp has
exceptional bioactive potentials such as osteoconductivity
and biocompatibility as it is the most resemblance to the
mineral composition of the bone tissue. Reports suggest
that Sr substitution into HAp can improve the biomaterial
properties, such as the crystalline nature and dissolution
rate under physiological conditions. Sr-substituted HAp
(SrHAp) shows osteoinductive properties with great solu-
bility (Fig. 4). The inclusion of Sr in the HAp structure has
positive and inductive impacts on cell growth and differen-
tiation, indicating the effectiveness of Sr for long-term use.
Alkaline phosphatase (ALP) is an important enzyme associ-
ated with the bone mineralization and represents as a use-
ful biochemical marker of bone formation [63, 64]. SrHAp
nanoparticles were also found to increase the ALP activity,
associated with the cloning process in hard tissues and there
improve the process of tooth remineralization [65] (Fig. 5).
Titanium (Ti) dental implants are used widely in clini-
cal practices, but they arise concerns regarding the risk of
prosthetic loosening and post-operative infection. Several
surface modifications have been used to overcome these
limitations. Titanium oxide nanotubes (NT-TiO 2) have
been researched extensively for their tubular shape and eas-
ily adjustable diameter. NT-TiO2 surface is modified by Sr
for targeted delivery. Its effects on better bone formations
and preventive bone resorption, make Sr an ideal element of
Fig. 4  Strontium-substituted
hydroxyapatite nanocomposite
as a bone cement to prevent
tooth decay
Page 5 of 15 25
clinical interest. It enhances replication of osteoblasts, dif-
ferentiation, and mineralization of the bone matrix through
a mechanism that depends on the calcium-sensing recep-
tor (CaR). Sr-loaded nanotubular structures (NT-Sr) were
hydrothermally treated to functionalize them as NT-TiO2 in
a solution of Sr(OH)2. These structures can provide long-
term, controlled release of S ­ r2+, leading to favorable osteo-
genic characters. Angiogenesis helps in bone healing and
bone regeneration to restore the effective supply of blood.
Improved angiogenesis at the site of the implant causes bet-
ter tissue assimilation and inhibits infection by inducing the
host immune system. Additionally, ­Sr2+ can induce osteo-
blast cells to secrete VEGF, having both angiogenic and
osteogenic activities. NT-Sr-Ag generated hydrothermally
can sustainably release S ­ r2+ and A­ g+, and the hydrothermal
treatment does not cause any change in the NT morphology
but changes amorphous ­TiO2 present in NT-Ag to cuboidal
­SrTiO3, which has little influence on the nanotubular archi-
tecture. However, the tube diameter was slightly decreased
with hydrothermal treatment time which may influence the
release of ­Sr2+ [66].
Maximum dental caries along with other dental prob-
lems are found specifically in the grooves and microc-
racks of posterior teeth, known as pits and fissures. These
regions offer bacteria to colonize and form plaque [67, 68].
Caries formation can be prevented by designing protec-
tive sealant materials for these areas, which are also found
to show effectiveness in protecting tooth decay [69, 70].
Although many materials are used as sealants [71], a mate-
rial that could prevent secondary caries at the interactive
face of tooth and the restorative compounds are still under
scrutiny [72, 73]. The large surface area of nanomaterials
bestowed them to be utilized to design restorative methods
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25 Page 6 of 15
Fig. 5  Strontium nanocomposite for prevention for dental caries
and therapeutics [70, 74, 75]. Strontium fluoride (­ SrF2)
nanoparticles have been found to play a protective role
against oral bacteria. Tooth decay can also be prevented
due to sustained release of fluoride, and to prevent second-
ary caries [76]. In a study, Bis-GMA-TEGDMA-UDMA
mixed monomers, ­SrF2NP, yattria-stabilized zirconia, and
poly-ε-L-lysine were mixed to develop a sealant. This seal-
ant provides physicomechanical and antimicrobial char-
acteristics to the sealant. It was observed that the S ­ rF 2
nanoparticles and ε-PL lead to positive interaction, lead-
ing to the enhanced bactericidal activity of the sealant.
The mechanical limitations can be remunerated by adding
proper proportions of Yttria Stabilized Zirconia nanopar-
ticles (YSZ NPs) to the sealants [77].
HApNP filled dental resins have drastically revolution-
ized the field of restorative dentistry, providing advantages
such as remineralization and enhanced polymerization.
However, these materials contain limited radiopacity pre-
venting secondary caries diagnosis. Thus, a novel radio-
paque dental adhesive was designed by the inclusion of
novel SrHApNP with improved radiopacity, easy tracking
of actual remineralization, and enabling detection of recur-
rent caries [78].
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Nanotechnology for Environmental Engineering (2021) 6:25
Drug delivery
The efficient delivery of an active drug molecule to the tar-
geted cells via an optimum route of administration is the
major problem in drug delivery systems. Besides this, the
adsorption/absorption of the drug molecule in the body
depends significantly on drug size; smaller size having bet-
ter absorption [79, 80]. The most frequent route of adminis-
tration includes oral, topical, transmucosal, and inhalation
due to preferential noninvasiveness. The effective delivery
through the oral route possesses challenge due to the nature
of the gastrointestinal tract. The carrier and the drug might
undergo degradation by pancreatic enzymes [81]. However,
the poorly water-soluble drugs have low bioavailability
because of their low adsorption capacity in the circulatory
system. Drugs with high aqueous solubility could increase
their local concentration, but cannot cross lipid-rich mem-
branes to achieve a pharmacological reaction. Mesoporous
materials have gained significant interest due to their large
surface area, uniformity, changeable pore size, and a large
degree of porosity [82]. Due to these advantages, attempts
have been made to produce such materials. Nanorods are
well-known to be used as a drug carrier for several antibiot-
ics, anticancer drugs, as well as bone substituents. Chitosan
Nanotechnology for Environmental Engineering (2021) 6:25
in recent years has shown promising characters such as
biocompatibility and mucoadhesive properties, emerged
as a useful drug carrier. In a recent study, chitosan-coated
mesoporous SrHAp nanorods were found suitable for the
delivery of a hydrophobic drug with no cytotoxic effects
[81].
The addition of strontium to other nanoparticles such as
silica enhances the drug delivery potential of the mesoporous
silica nanoparticles [57]. Mesoporous SrHAp nanorods with
luminescence-functionalization having self-activated lumi-
nescence (360–570 nm), ibuprofen was loaded, to generate a
multifunctional compound to track and monitor the process
of drug release [83]. Strontium-doped A ­ g2O nanoparticles
were examined for DNA interactive studies and can increase
the amount of the Sr up to 5%, leading to the increased bind-
ing affinity of the NPs [84].
As a novel biodegradable nanosystem, strontium carbon-
ate nanoparticles (SrCNPs) were developed for delivering
the anticancer drugs and ensuring their efficient release
depending on the pH of the target environment. This creates
a smart system for drug delivery in an acidic environment,
specifically in the tumor microenvironments. An anticancer
agent, etoposide was loaded efficiently on the nanoparticles.
The drug-loaded SrCNPs showed more potential antitumor
activity than the free drug alone. However, it was also found
that the blank SrCNPs were nontoxic to the normal cells,
which ensures their targeted delivery [85].
Antimicrobial agents
Green synthesis of mixed strontium cerium oxide (SrO-
CeO2) nanoparticles using ionic liquid (IL) assisted an etha-
nolic extract of Pedalium murex plant showed antibacterial
activity to both Gram + ve and –ve bacteria. SrO-CeO2-
combined NPs are more susceptible to Gram –ve bacteria.
The toxic behavior was exerted because of the high site
vacancies of oxygen, production of reactive oxygen species
(ROS), very small particle size, and large surface area [86].
To increase the effectivity of the HApNP, strontium half
(SrCaHAp) and substituted (SrHAp) nanoparticles were
synthesized, where the calcium was substituted with stron-
tium. The HAp and SrCaHAp nanocomposites were found to
exert antibacterial properties at a lower concentration toward
Escherichia coli, Staphylococcus aureus, and Lactobacil-
lus species. SrHAp nanoparticles show antibacterial activity
at a very minimal concentration as compared to SrCaHAp.
Altogether suggest SrCaHAp can be useful for the treatment
of dental caries (Fig. 4) [87].
The novel strontium titanium ferrite ­(SrTi1−xFexO3-δ or
­STFx) composite is a solid solution between strontium titan-
ate ­(SrTiO3 or STO) and strontium ferrite (­ SrFeO3-δ or SFO)
[88]. Perovskite S­ TFx metal oxide nanoparticles arise as a
Page 7 of 15 25
potential photocatalyst for antibacterial application, and the
effectiveness was exerted by a S ­ TF0.8 probe from the killing
of a large bacterial load of E coli in a very short time. The
opposite surface charge, alkaline pH, dissociation of Sr ion,
and the small size of the S ­ TF0.8 nanoparticles have better
antibacterial effect. Thus S ­ TFx is used potential antimicro-
bial agent for disinfection of water [89].
SrONPs were synthesized via a microwave technique
using strontium nitrate and Ocimum sanctum leaf extract.
This is a low-cost, convenient, eco-friendly, and effective
technique for the biosynthesis of SrO NPs. Moreover, the
synthesized SrO NPs demonstrated effective antibacterial
activity against Gram − ve bacteria such as Proteus vulgaris,
Psudomonas aeruginosa, Morganella morganii, and Kleb-
siella pneumonia than that of the Gram + ve bacteria [90].
Strontium-fabricated ­Ag2O nanoparticles show less cytotox-
icity, antibacterial activity, a good antioxidant, and antifun-
gal activities in comparison with naked A ­ g2O nanoparticles
[84]. SR-loaded poly d,l-lactic-co-glycolic acid (PLGA)
microspheres (PM) were successfully synthesized and
incorporated with a silver (Ag) and hydroxyapatite (HAp)
nanoparticles to achieve osteoconductivity and antibacte-
rial properties [91]. This nanocomposite greatly increases
osteogenic differentiation potential and exerts excellent
bactericidal properties. SR-PM-Ag-Hap is biocompatible
for drug delivery, osteoinductive potential, and antibiosis,
to make bone-related infections and induction at the site of
infection [91].
Effective immunotherapy
There are diverse mechanisms through which the nano-
particles exert immune responses against antigens, which
include immune stimulation by direct antigenic delivery
to the immune cells [92]. To create a stable and prolonged
effect of the antigen on the immune system, it is neces-
sary to release the antigens slowly [93]. Allergen-specific
immunotherapy (ASIT) is often used to treat allergies [94].
Dendritic cells (DCs) act as primary cells to exert adaptive
immune response for an effective ASIT. Several subtypes of
DCs have separate functional properties, from induction of
tolerance to stimulation of accurate immune responses [95].
Strontium-doped hydroxyapatite porous spheres (SrHApS)
were checked for their potentiality to be used as a matrix
to prolong the local delivery of protein antigen. The find-
ings showed the use of SrHApS in ASIT can mitigate the
targeted delivery of allergen to DCs and thereby increase
the efficiency of ASIT. SHAS was loaded with an allergen,
ovalbumin (OVA), that increased the integrity and stabil-
ity of OVA, creating a slow-release and the depot effect,
resulting in continued immunologic responses when applied
in vivo [96].
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25 Page 8 of 15
Treatment of diabetes
Diabetes is a metabolic disorder accompanied by multiple
factors with subcutaneous administration of insulin being
the most frequently used therapy [97]. Persistent insulin
release is thought to be of considerable importance to elicit
long-term glycemic control by decreasing the frequency
of injections. Nanoparticles of carbonate apatite have the
potentiality of being used for sustained insulin release as
responsive nano-carriers. Strontium-incorporated carbonate
apatite particles prepared and compared with unmodified
apatite for the ability to bind insulin followed by its sub-
sequent release [98]. The strontium incorporated particles
were shown to have enhanced electrostatic affinity toward
insulin and promote the slow release of insulin by preventing
the initial burst phase [98].
Calcium ions are used to release insulin by physiological
stimuli [99]. However, the specificity of calcium require-
ment has not been completely established. The effects of
­Sr2+ ions on the function of pancreatic B cells were studied
[100]. It was reported that ­Ca2+ replacement by ­Sr2+ did not
alter glucose-induced insulin release from the rabbit pan-
creas incubated under glycemic control, as well as induction
of electrical activity in mouse islets. However, the findings
showed that ­Sr2+ is less effective than ­Ca2+ in releasing
insulin [84]. Glucose-induced insulin release can be attrib-
uted to an elevated cytoplasmic C ­ a2+ in pancreatic β-cells
because of the opening of voltage-gated ­Ca2+ channels of
the plasma membrane [101, 102]. Rhythmic ­Ca2+ signals are
synchronized within and between the islets and thus produce
a pulsatile release of insulin in the circulatory system [103,
104]. The oscillatory signal-induced release was investigated
in collected pancreatic islets and β-cells from human cadav-
eric organ donors. By using S ­ r2+ as a substitute for C
­ a2+,
glucose-stimulated rhythmic activity of insulin in individual
β-cells was demonstrated [100].
Impaired healing and nonunion of skeletal fractures are
global public health problems, with morbidity exacerbated
in type 2 diabetic (T2DM) patients. T2DM has been clini-
cally recognized to increase the risk of infection, malunion,
nonunion, and re-operation across a wide range of surgi-
cally treated fractures [105]. Fracture healing is a complex
process, initiated by an inflammatory response, followed by
the formation of soft and hard callus and ending with callus
remodeling and replacement with the lamellar bone [106].
This series of events follows an organized spatial and tem-
poral sequence of events and might be affected by factors
including abnormal glucose and estrogen levels, and thus,
T2DM pathophysiology can severely affect these processes.
The effects of SR combined insulin on the healing pro-
cess of a fracture model in OVX rats having T2DM by
feeding high-fat diet and streptozotocin were investigated
[107]. SR combined with insulin raised the expression of
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Nanotechnology for Environmental Engineering (2021) 6:25
osteogenic-specific markers in the callus; however, it did
not show any additional radiological benefits on new callus
formation compared to insulin alone. Insulin-incorporated
SrHApNPs were investigated for efficient adsorption of insu-
lin. It was shown that the SrHA surface did not cause any
alteration in the native conformation of insulin. However,
cell culture studies done in vitro using F-OST stromal cells
demonstrated improved cell proliferation by insulin-loaded
SrHA [108].
Application of strontium nanoparticles
in environmental science
Wastewater management
The rapidly growing industries, and the discharge of the
metal pollutants into the aquatic body and sources of water,
have raised environmental concern globally [109–112].
Heavy metal ions can be extremely toxic and carcinogenic
[113, 114]. The abundance of some organic, as well as
inorganic elements in water, is a vital factor since it affects
the quality of water. Frequent discharge of toxic pollutants
in water obtaining resources causes an elevation in their
amount and can be extremely harmful to human health as
well as affects agriculture [115, 116].
Among the pollutants, nitrate a potential inorganic con-
taminant that raises concern in the safe water supply [117].
Nitrate is highly soluble in water and causes easy leakage
and vast contaminating effects like eutrophication [118],
teratogenic effects on aquatic organisms, and methemo-
globinemia in infants [118, 119]. Activated carbon (AC)-
based adsorption is used for nitrate removal due to its high
surface area which can trap the nitrate anions easily. How-
ever, AC comprises of limited activated sites and has a dif-
ficult process of regeneration. Oxides of earth metals, such
as strontium oxide, are a potential material for the treatment
of water due to their positive charge and ability to adsorb
minimal concentration of anionic analytes. The assemblage
leads to the removal of nitrate. Moreover, a combination
of AC decreases aggregation of the decontamination phase
and increases decontamination abilities. A study showed
that a novel nanocomposite was developed depending on
iron oxide-doped AC and strontium oxide (FeAC-Sr) exerted
high removal potentiality toward nitrate among various ani-
ons and cations and can be utilized for chemical remediation
of underground water [120]. Strontium ferrite (SrFe) has
stable physicochemical characteristics and was used for the
determination of nitrite, which showed superior sensitivity,
stability, and reproducibility [121]. A cost-effective, eco-
friendly tri-metallic magnetic ferrite ­Sr0.3Mg0.7Fe2O4 (SMF)
mesoporous nanocubes were synthesized by using castor
oil polyol, an effective solvent, surfactant, and template.
Nanotechnology for Environmental Engineering (2021) 6:25 Page 9 of 15 25

It shows excellent adsorption capacity against congo red and pharmaceutical industries. Antibiotics like, tetracy-
dye under-stimulated conditions, with good recycling abil- cline, cefotaxime are used illegally in food preservations
ity. The enhanced kinetics of adsorption, thermodynamics may have various side effects such as nausea, diarrhea,
property offer it as a unique dye adsorbent [122]. skin rash, body aches. Thus, the uncontrolled use of these
Cadmium (Cd) is a hazardous metal and its long-term antibiotics creates a lot of health-related issues. These
exposure to cadmium results in accumulation in the kid- antibiotics may create other environmental toxicity on
ney, causing renal tubular damage. Cd causes a disordered other organism as well. Moreover, the release of antibi-
in calcium metabolism, hypercalciuria, and kidney stones otic molecules in the environment can give rise to resist-
[123, 124]. Porous nano-barium strontium titanate adsorbent ant microorganisms. Strontium titanium trioxide (­ SrTiO3)
was found to have the ability to adsorb cadmium from water nanoparticles have been investigated extensively for water
through an endothermic and spontaneous physical process. treatment because of their chemical and thermal stability,
Thereby, this material can be used for cadmium ions removal photocatalytic activity, large surface area, and large car-
from contaminated water [125]. rier effective mass. ­SrTiO3-doped graphene oxide (GO)
Ammonia belongs to a useful nitrogen species used in provides an eco-friendly and thermally stable low-cost
industry [126, 127]. Thus, it must be removed completely nanocomposite. ­SrTiO3-based nanocomposites show poor
from water bodies before release into domestic, urban, agri- adsorption of material. Thus, a newly synthesized gra-
cultural, or industrial wastewater [128, 129] as it is highly phene oxide-magnetic nanoparticles-SrTiO3 (GO-MNPs-
toxic, might lead to eutrophication and corrosion, decreases SrTiO3) was shown to increase tetracycline and cefotaxime
oxygen transfer in the bloodstream resulting in major health adsorption from water [144] (Fig. 6).
hazards [130–132]. Although many methods have been
adopted to efficiently remove ammonia from wastewa- Agriculture
ter including traditional biological and chemical removal
methods, the use of adsorbents has raised as an attractive In different tropical climates, the amount of Ca, Mg, K, P,
approach due to its several advantages which include effi- and N amount varies in the soil. Soils in semi-arid and arid
cacy, simple formulations, and capacity to reduce sludge subtropical regions are scarce in Phosphate and micronu-
using photocatalytic activity [129, 133–136]. Strontium trient transition metals which include iron, copper, manga-
oxide/graphene oxide (SrO/GO) nanoparticles can remove nese, and zinc [145–147]. Two elements namely, Mg and
ammonia from industrial wastewater. The nanocomposite Ca essential for plant growth, and their uptake into the plant
showed a removal efficiency of 74.5% for ammonia among are much required during deficient conditions. Strontium
different co-existing ions. This nanocomposite is used as utilizes the same mechanism of cell entry as Ca and Mg
an alternative adsorbent for wastewater management [137].
Arsenic ions as a toxic and non-degradable metallic ion
can build up in groundwater, food chain well as and liv-
ing tissues thus can cause some health-threatening condi-
tions in humans [138, 139]. Strontium-based nanoparticles
­(SrTiO3) are used to decompose and adsorb the pollutants
[140] because of the rigid-particle spacers that give them
larger surface areas [141]. Polyaniline (PANI) is a poly-
meric material, widely investigated because of its nota-
ble physicochemical properties, such as thermal stability,
high conductivity, ease of production, low cost, and vari-
ety of usage [140]. Polyaniline-strontium titanium oxide
was converted to magnetic polyaniline and strontium-
titanium (MP-SrTiO3) by adding F ­ e3O4NPs. MP-SrTiO3
can be used to remove ionic arsenic (III) from water. Due
to the cationic polyaniline backbone, the positive charge
of the SrNPs, they can adsorb analytes exhibiting negative
charges [142, 143]. The high removal efficiency showed
the potentiality of using this technique for large scale pro-
duction of nanomaterial for arsenic removal from environ-
mental samples with high efficiency [139].
Many antibiotics are frequently discharged into water Fig. 6  Strontium-based nanoparticles to be used in wastewater man-
bodies through municipal wastewater treatment plants agement

13
25 Page 10 of 15
does, such as transporters of the cell membrane. Sr can
reduce Ca and Mg content of the plant tissue as it replaces
Ca. Alternative studies have shown that Sr is not able to
replace Ca in cell division in algae, Carteria sp. and forma-
tion of grain in Avena sativa and Triticum aestivum. Ca- and
Mg-substituted strontium nano-hexaferrites (SrMgCa nano-
HF) were investigated for their effect on nutrient uptake
and physiology of barley (Hordeum vulgare L.) [148].
The results show that the substituted Sr nano-hexaferrite
caused increased rate of germination, tissue growth, amount
of chlorophyll pigments, and soluble protein content. The
traces of the substituted elements were also detected in plant
leaves increasing the magnetic signals. Overall, the study
shows the internalization of the four elements into the plant
through substituted nano-HF. The finding suggests mineral-
substituted nanoparticles can have a significant impact on
breeding programs for, 1) improvement of seed germination
and, 2) treatment of mineral-deficient plants. Nanoparti-
cles produced ROS helps to degrade the seed cover and
upsurge the rate of germination [149–151]. ZnO and TiO2
nanoparticles increased germination in Cicer arietinum by
increased generation of reactive anions, which indirectly
helps in water accumulation and increased rate of oxygen
uptake required for fast germination [152]. ZnO and TiO2
nanoparticles increased germination in Cicer arietinum by
increasing reactive anions, which helps in water accumula-
tion and increased rate of oxygen uptake [153]. Treatment
of nanoparticles increases the penetration ability of seed
coat, cell wall, and organelle or cell membrane and thus the
germination rate [154, 155].
Seed germination is linked to various metabolic, cel-
lular, and molecular processes. The germination process
can be divided into two phases; the imbibition phase that
begins immediately after the seed comes in contact with
water and the later phase, called the activation phase is
characterized by a number of metabolic changes [156]. The
metabolic reactivation followed by seed imbibition provides
an important source of ROS [157]. ROS is produced con-
tinuously during germination and has often been known to
produce negative effects. However, their production is regu-
lated tightly by the balance between their generation and
scavenging, the ROS has now appear to have beneficiary
role in seed germination [158]. Such positive role results
from interaction between ROS and the hormonal signal-
ing pathways, resulting in alteration of gene expression or
intracellular redox status. This changes the perception of
the external factors by seed during germination, acting as a
signal that controls the successful completion of germination
[159]. Reactive oxygen species, such as, hydrogen peroxide
[160–162], nitric oxide [163, 164], hydroxyl radicals [161],
and superoxide radicals [161], get accumulated during seed
germination. Intracellular ROS regulates the cellular redox
state, results in protein oxidation and triggers the expression
13
Nanotechnology for Environmental Engineering (2021) 6:25
of specific genes [159] and also helps to protect the seedlings
against pathogens [165].
ROS interacts with plant hormones, such as abscisic acid
(ABA), gibberellic acid (GA), ethylene, auxin or brassi-
nosteroids, which have role in the seed germination and
dormancy [166, 167]. The relationship between ­H2O2 and
ABA is well documented, where ­H2O2 inactivates ABI1 and
ABI2 type 2C phosphates. Reductions of endogenous level
of ABA alleviate seed germination [168–171]. Transduction
pathways of ROS and ethylene share common components,
and GA3 modifies the redox status of aleurone during ger-
mination. ROS stimulates the genes involved in GA signal-
ing, which further suggest its role in controlling germination
process [165].
Plants uptake essential nutrients from soil, and thus, if an
essential nutrient is absent from the soil, it makes the plants
nutrient deficient. Previous studies have shown that nano-
particles can promote nutritional status of plants [172]. For
instance, ZnO nanoparticles found to increase Zn content in
wheat and maize [173, 174], manganese iron-oxide nanopar-
ticles increase the level of Mn and Fe in barley [175]. In a
study, Rui et al. proposed the use of iron oxide nanoparticles
as a fertilizer, to enhance peanut plant growth [176].
Plants produce small molecules known as secondary
metabolites, which include toxoids, phenolic acids, tarpe-
noids, steroids, polysaccharides, flavonoids, alkaloids, etc.
[177]. Various external factors such as, soil, water quality,
light and temperature can alter the amount of accumulated
plant secondary metabolites [177, 178]. A study investigated
the role of Sr on the production of phytoestrogens in soy-
beans. ­Sr2+-modified Hoagland’s solution (concentration of
­Sr2+ varied from 0.5 to 3.0 mM) treated plants showed a
significant increase in the concentration of phytoestrogens
(which was found to be elicited upto 3.77 fold) in all concen-
trations of Sr treatment, which was maximum at a concen-
tration of 2 mM ­Sr2+ [179]. Phytoestrogens naturally occur
in fruits, vegetables thus found in our dietary supplements
[180]. Although they are plant-based, phytoestrogens act
much like mammalian estrogen. When phytoestrogens are
consumed, our bodies may respond as estrogen [181]. Soy
(Glycine max (L.) Merr.) is widely used in pharmacy for
alleviating the symptoms of osteoporosis. Biofortification
of soy with ­Sr2+ has been found to enhance the level of phy-
toestrogens [182, 183].
Toxic gas sensing
Volatile organic compounds (VOCs) are toxic pollutants that
might have a severe effect on human health. VOCs emis-
sion can be controlled by low-temperature catalytic combus-
tion. Different types of substances such as noble metals and
metal oxides have been studied in this regard. Toluene is an
important volatile compound and a novel strategy adopting
Nanotechnology for Environmental Engineering (2021) 6:25
the combination of citric acid complexing, and hydrothermal
treatment was developed to design strontium-doped lanthanum
cobalite and magnetite as very active catalysts for the total
oxidation of toluene [184]. Strontium ferrite nanomaterials can
sense the existence of gases like acetone vapors, ethanol, and
ammonia [185].
Conclusion
The science of nanotechnology is changing with ever increas-
ing knowledge about the novel nanomaterials. Strontium nan-
oparticles, as novel metallic nanoparticles, have thus gained
significant importance in various sectors. Having similarities
with some of the important trace metals, such as calcium and
magnesium have strontium-based nanomaterials have exclu-
sive properties that are helpful in bone and tissue engineering
applications. Several dental implants have also utilized the
properties of strontium nanocomposites to design implants,
dental cement to prevent dental fractures, microbial contami-
nation of the implant as well as to prevent secondary caries
formation. These nanoparticles show antimicrobial activity.
As an emerging field of research, the nanocomposites of stron-
tium substituted materials are gaining increasing attention as
anticancer, immunotherapeutic agents as well as an effective
inducer of insulin release. Strontium-based nanocomposites
have also found their potential application in the field of agri-
culture for supporting plant growth by providing strontium
as an essential element, along with wastewater management,
which is also linked directly with the agricultural system as
well as human health. The potentials of Sr nanomaterials still
need to be explored and deserve notable attention for the ben-
efits of the human being.
Acknowledgements MM laboratory is thankful to SERB/
EMR/2017/003054, BT/PR21857/NNT/28/1238/2017 and Odisha
DBT 3325/ST(BIO)-02/2017 for financial assistance.
Declarations
Conflict of interest All authors declare that they have no conflict of
interest.
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