Quantum Dots for Medical in vivo NANOTECHNOLOGY AND INNOVATION

Imaging A.Y. 2019/2020

ALESSANDRO GHIRARDI
Quantum Dots(QDs)

 NCs of semiconductor materials

 Size-Tunable properties

 0-D structures
 Fig.(A) Scanning transmission electron micrographs of PbSe quantum dots: low resolution (full scale = 320
nm) showing the ordering of an ensemble of nanocrystals. 

The structure

o A core of a semiconductor, groups II–IV (CdSe)

or groups III–V (InP)

o The shell is a higher bandgap material (ZnS)

o A capping outer layer

 Properties
I
I
 Tunable fluorescence emission

 Broad absorption spectrum λ (nm)

Fig.(A) Emission spectra as a function of the QD size distribution with the same composition; the colored
circles represent particle size. (B) absorption and emission spectra of QDs.
 Large Stokes shift

 Photostability

 Active surface for chemical conjugation.

 A Tunable
Bandgap

Radius of the semiconductor nanocrystal is

smaller than the exciton Bohr radius

Quantization of the energy levels

Quantum confinement.
 NB: Only when size of the dot is close to or below the Exciton Bohr Radius.

 Decresing size of QDs, will grow up

 More energy to excite the dot, and, more energy

released
 color shift from red to blue in the emitted light

 [ = QDs dimension].   h2 𝜋 2
𝐸𝑒h =𝐸 𝑔 + ∗ 2
− 𝐸𝑐𝑜𝑢𝑙
2𝑚 𝑣 ,𝑐 𝑑
 QD’s application

The photoluminescence (PL) of QDs makes them

candidates for biomedical imaging and therapeutic
interventions.

QDs conjugated with cancer specific

ligands/antibodies/peptides are effective for detecting
targeting and imaging human cancer cells.
Classical problems for
imaging
Dyes have narrow absorption, broad emission spectra, low brightness

• Lack in sensitivity or specificity

• Tissues “problems”

QDs ranging from 700 to 900 nm.

• Autofluorescence is minimal

Fig. organic dyes vs Dots absorption and emission

spectra
 Why Quantum
Dots? Fig.A Excitation decay of organic
fluorophores and QD. The time
constant of the QD is longer than
the one of the organic
 Resistance to degradation fluorophore. 

 Fluorescence time

 Large Stokes shift reduces autofluorescence

Fig.B Color of light depends on

size quantum dot.
 Used for the multicolor detection with a single
wavelength excitation source
 Why Quantum
Dots?
 Aggregation

 Traps & Blinking

 Biconjugation leads problem with targeting

QDs suffer from surface trap states which influence their optoelectronic properties. These trap
states act as non-radiative recombination centres and lowers the PLQY of the dot
 Cytotoxicity e.g. Cdse
 Types and Fig 1: Fluorescence
imaging of tumor
with uptake of

functionalization of 6PEG-Ag2S QDs.

Half-life of
circulation of 4.37

Imaging
± 0.75 h.

QDs used to observe multiple systems in

vivo noninvasively due to the surface chemistry

This allows the tailoring of QDs to target desirable

structures  

Cell, Vasculature and Tissues

“QDs imaging for
embryonic stem
cells”
QDs for their photostability

 After day 2, cells labeled with QD 525 to 705 could

not be detected in vivo

 QD 800 signal could be detected up to 14 days in

animals post injection (higher extinction coefficient
and wider emission spectra within NIR)

Embryonic stem cells with six different QDs using a single excitation wavelength (465 nm) . QD 800 offers
greater fluorescent intensity than the other
 “In Vivo Fluorescence
Imaging with QDs in
II-NIR”

QDs for in vivo imaging of vasculature

• Tracing of blood flow and view of blood vessels

to understand pathogenic processes including
cancer metastasis
(a) In vivo fluorescence images of CdSe/ZnS QDs, ICG, and Ag2S QDs into mice .The green-yellow
signal (CdSe/ZnS QDs) indicates the strong autofluorescence of tissues in the visible emission window.
The red signal concentrated in the liver with ICG indicates the short blood circulation half-time. The red
signal widely distributed in the whole body with Ag2S QDs indicates the long blood circulation half-
time.
“NIR QDs labelled
for imaging”

Mice injected with NT4 peptide-QDs,promising for

cancer theranostics, and N-QDs

• At 1 h, nude QDs only showed background

fluorescence(318:1) Fluorescence intensity (a) and tumor-to-background ratio (b).
Monitoring of tumor fluorescence intensity showed that as early as 0.5 h post-injection, the
• Tumor targeting by NT4-QDs induced much fluorescent signal of NT4-QDs and unlabelled QDs appeared in the tumors with higher
higher retention of QDs at the tumor site than by fluorescent intensity of the latter with respect to the former (Fig. 6a).
nude QDs
• Possible applications in intraoperative image-
guided surgery.
Features for better
Imaging
 Coating
Stabilize QDs

Longer circulation (3 hrs) than organic dyes(min)

Makes QD large enough to avoid renal filtration

 NIR imaging properties

Minimizes autofluorescence
Deeper penetraton into tissues
 Still problems to Developements
be solved
 Heavy metal QDs have cytotoxic effects  Heavy metal-free (indium) QDs with a good QY and fast
localization (minutes)

Cost of synthesis

X Large CdTe, PbS or PbSe QDs V Some type-II configuration of InAs QDs (InAs with ZnSe shell
for e.g.)
Chen C, Peng J, Sun SR, et al. Tapping the potential of quantum dots for personalized oncology: current
status and future perspectives. Nanomedicine (Lond) 2012; 7: 411-42

Chen LD, Liu J, Yu XF, et al. In-vivo targeted imaging of hepatocellular carcinoma in nude mice using quantum dot
probes. Zhonghua Bing Li Xue Za Zhi 2007; 36: 394-399

Tapping the potential of quantum dots for personalized oncology: current status and future perspectives.Chen C, Peng J,
Sun SR, Peng CW, Li Y, Pang DW Nanomedicine (Lond). 2012 Mar; 7(3):411-28.

Near-infrared quantum dots labelled with a tumor selective tetrabranched peptide for in vivo imaging
Jlenia Brunetti, Giulia Riolo, Mariangela Gentile,  Andrea Bernini,  Eugenio Paccagnini,  Chiara Falciani,
Luisa Lozzi,  Journal of Nanobiotechnology volume 16, Article number: 21 (2018) 

QDs imaging for embryonic stem cells

Published: 9 October 2007 BMC Biotechnology 2007, 7:67 doi:10.1186 © 2007 Lin et al.; licensee BioMed Central Ltd.

In Vivo Fluorescence Imaging with Ag2S Quantum Dots in the Second Near ‐Infrared Region
Hong, Guosong , Robinson, Joshua , Zhang, Yejun , Diao, Shun, Antaris, Alexander . Angewandte Chemie 2012/09/01 -124

Extra slides
 Metal Nanoclusters (NCs) for imaging

Advantages over QDs

-Low toxicity
-Easy synthesis and
functionalization
-Good water solubility

Sci. Rep, 2013 ,3. 1157; Nanoscale, 2013,5, 1009-1017 Angew. Chem. Int. Ed. 2013, 52, 12572 –12576
Quantum Dots (QD) synthetic
approaches
High Temperature Route
 Highly crystalline QD
 Mono-disperse, narrow size distribution
 Easy core/shell growth control
 High quantum yield, up to 90%
 Post surface modification

Low Temperature Route

v Water-soluble, no post synthesis surface modification
Not highly crystalline TEM image
Broader size distribution
Difficult to make core/shell QDs
Low quantum yield: typically < 15%
(with exceptional ~ 45%)
“QDs for oncology:
status and future
perspectives”

Animal imaging by injecting human

hepatocellular (HCCLM6) carcinoma cell
lines witch overexpress specific proteins with
QD-IgG probes.

HCCLM6 helps in the construction of a

platform for the early monitoring of liver
cancer metastasis

[A: The imaging system for living animal models. B: In vivo targeted imaging of the subcutaneous tumor
model and site-by-site spectra analysis of the tumor, .
C: In vivo targeted imaging of liver cancer lung metastasis]