applications of quantum dots in medicine Pharmacy and pharmacology Bioimaiging (in vitro labelling , in vivo imaging) Tumor & cancer target Pathogen and toxin detection Photothermal therapy (PTT) photodynamic therapy (PDT) Targeted surgery Immunoassay DNA analysis biological monitoring drug discovery

2. Quantum Dots
and Application
in Medical
Science
By: Hashem Ghezelsofla

3. 3

4. 4
Quantum confinement
effects give rise to unique
optical and electronic
properties in QDs, giving
them numerous
advantages over current
fluorophores, such as
organic dyes, fluorescent
proteins and lanthanide
chelates.
Properties that
particularly influence
fluorophore behaviour,
and therefore applicability
to different situations,
include the width of the
excitation spectrum, the
width of the emission
spectrum, photostability,
and the decay lifetime.
The narrow emission and
broad absorption spectra
of QDs makes them well
suited to multiplexed
imaging, in which multiple
colours and intensities
are combined to encode
genes, proteins and
Optical properties of quantum dots

5. 5
Time dependence of
the fluorescence
intensity of silanised
nanocrystals and
rhodamine 6G at 488
nm.
The nanocrystals
exhibit a stable
emission for at least 4
h, while the dye
bleaches after 10 min,
colours correspond to
nanocrystal emission,
R6G is in black

6. 6
 Pharmacy and pharmacology
 Bioimaiging (in vitro labelling , in vivo imaging)
 Tumor & cancer target
 Pathogen and toxin detection
 Photothermal therapy (PTT)
 photodynamic therapy (PDT)
 Targeted surgery
 Immunoassay
 DNA analysis
 biological monitoring
 drug discovery
applications of quantum dots in medicine

7. 7
Drug delivery
QDs can be cross-linked to biomolecules such as peptide, antibodies, or small-molecule ligands to make them specifically a target to biological systems and therefore be
used for diagnosis and targeted drug delivery. Fe3O4 NPs are embedded in a spherical polystyrene matrix to fabricate magnetic nanospheres (MNSs) and then
conjugated NIR QDs onto the surface of the MNSs. For drug storage, the chemotherapeutic agent paclitaxel (PTX) was loaded onto the surface of these MNSs utilizing a
layer of biodegradable poly(lactic-co-glycolic acid) (PLGA). Further attachment between the anti-PSMA and PTX-PLGA-QD-MNSs was achieved using
ethylenediamine by conventional EDC/NHS bonding tactics .Some pivotal parts are involved in such novel architectures that are fluorescent superparamagnetic NPs,
tumor-specific antibodies, and anticancer drugs, and they are used for multimodal imaging and hyperthermia, cell targeting, and local therapy purposes, respectively

8. 8
The ZnO QD-based pH-responsive drug delivery platform for intracellular controlled release of drugs was developed. PEG was introduced into NH2-ZnO QDs (PEG-
ZnO), which were stable under physiological conditions and HA molecules were bound to HA-ZnO QDs (HA-ZnO-PEG) for targeting HA-receptor CD44-specific
cells. The doxorubicin (DOX) molecules were successfully loaded onto PEG-functionalized ZnO QD by forming metal-ODX complexes and covalent interactions. The pH-
sensitive ZnO QDs were dissolved in acid endosomes/lysosomes after the uptake of cancer cells, thereby triggering dissociation of metal–drug complexes and controlled
DOX release. As result, a synergistic therapy was achieved owing to incorporation of the antitumor effect of Zn2+ and DOX (Fig.). They were subjected to the receptor-
mediated endocytosis and released inside the cancer cells murine colon adenocarcinoma tumor C26, which indicated that these tumor-targeting drug delivery systems
are meaningful for future cancer therapy.

9. 9
Bioimaiging

10. 10
Cell and tissue imaging
Dubertret et al. encapsulated QDs in phospholipid block-copolymer micelles.
Further, these QD micelles were added to Xenopus embryos at the blastomere stage; these micelles remained
in the injected cells until cell division and were found in the descendants of cells .
Only concentrations higher than 5 × 109 QDs per cell caused abnormalities. In addition, the nanocrystal
fluorescence could be followed to the tadpole stage, which allows tracing the cell lineage in embryogenesis.
This was a successful exploration in tissue image. years, WGA-QD-NPs are also involved in drug delivery.

11. 11
Cell and tissue imaging
Yukawa et al. reported that labeling of QDs using R8 could be used for imaging
ASCs.Results of this study are meaningful for regenerative medicine. Delivering
imaging agents to the brain plays a vital role in the area of diagnosis and treatment of
diseases related to the central nervous system (CNS), as well as explains their
pathophysiology. TOPO-QDs were entrapped into the core of poly(ethylene glycol)-
poly(lactic acid) NPs and the resulting NPs were functionalized with Traut’s reagent-
thiolated wheat germ agglutinin (WGA) through maleimide groups at the ends of the
poly(ethylene glycol) (PEG) spacers to manufacture WGA-QD-NPs. After being
injected into the nasal cavity, WGA-QD-NPs could gain access to the regions with
disorder in the CNS through the nasal mucosa and can remain in the brain longer than
4 h. In recent years, WGA-QD-NPs are also involved in drug delivery

12. 12
Tumor imaging
Wu et al.revealed that VEGFR2–CD63 signaling is the key factor mediating entry of the functionalized InP nanocomposite (IMAN) into cells.
It indicated that the IMAN may provide a new and promising chemotherapy strategy against cancer cells, particularly by its active targeting
function and utility in noninvasive three-dimensional tumor imaging .These examples show that the combination of versatile QDs with powerful
techniques could result in great breakthroughs in the current understanding of tumor biology, improve early detection schemes, and create
avenues for treatment.
Schematic diagram of applying the IMAN for targeted tumor imaging and treatment.

13. 13
Images of tumor cells labeled by QDs. (A) MDA cells were labeled by anti-CD71-QDs (B) HeLa cells were labeled by transferrin-QDs.

14. 14
Vasculature imaging
(a) NIR-II fluorescence images of the nude mouse blood flow after injection of PEGylated Ag2S
QDs at different time (2.45, 3.3, 4.75, 7.5, 19.5, and 76.2 s).
(b) Magnified fluorescent image of vasculature in the nude mouse.
QDs have been used to
passively image the
vascular systems of
various animal models .
In an initial attempt along
this line, two-photon
imaging of vasculature
through the intact skin
and adipose tissue in
living mice has been
reported with water-
soluble CdSe/ZnS QDs
Further, although
fluorescent probes in the
second NIR window (NIR-
II) with Ag2S sDQ
edivorphgihartlulaitaps
noituloserrofgnikcart
sisenegoignadetaidemyb
aynit,romuttinacosla
ebdesunilacigrus
stnemtaert.nIsiht,krow
,ylbatondetalyGEPgA2 S
QDs with appropriate half-
life of 4.1 h in the blood
circulation remain bright
and are localized in the
body for more than 9 h ..

15. 15
Photoluminescence microscopy images of the lymph nodes flow after injection of CFQD® at different time
(A): 5 min, (B): 1 h, (C): 4 h, (D): 48 h, (E): 5 days, and (F): 10 days.
G: images from the control rats without QD injection.
Lymph node imaging
Intraoperative lymph node mapping (LNM) is highly significant for many surgeries in patients with cancer and draws extensive attention. QDs, as a
new fluorescent label compound, have been successfully used in the imaging and localization of lymph nodes in recent years. Using
photoluminescence, images showed the bio CFQD® NPs, when injected subcutaneously into the paw of rats, imaging of regional lymph nodes

16. 16
Esophageal sentinel lymph node mapping in pigs.
Showing original colour, QD fluorescence and false-colour QD fluorescence merged with original image

17. 17
viral diagnosis
Rapid and sensitive diagnosis of Respiratory
Syncytial Virus (RSV) is important for infection
control and development of antiviral drugs.
Antibody- conjugated nanoparticles rapidly and
sensitively detect RSV and estimate relative levels
of surface protein expression.
A major development is the use of dual-colour QDs
or fluorescence energy transfer nanobeads that
can be simultaneously excited with a single light
source.
A QD system can detect the presence of particles
of the RSV in a matter of hours. It is also more
sensitive, allowing detection of the virus earlier in
the course of an infection. When an RSV virus
infects lung cells, it leaves part of its coat
containing F and G proteins on the cell’s surface.
QDs have been linked to antibodies keyed to
structures unique to the RSV coat. As a
result,when QDs come in contact with either viral
particles or infected cells they stick to their surface.

18. 18
photodynamic therapy (PDT)

19. 19
Photothermal therapy (PTT)
The photothermal therapy (PTT) is a treatment that uses materials with high light heat conversion efficiency.
Zhang and coworkers have successfully synthesized novel, multifunctional, zero-dimensional to two-dimensional (0D–2D) RGD-QD-MoS2
nanosheets (NSs) with excellent fluorescence, photothermal conversion, and cancer-targeting properties by functionalizing single-layer MoS2 NSs
with fluorescent QDs and RGD-containing peptides, and PTT of human cervical carcinoma (HeLa) cells were achieved .

20. 20
QD interaction with liver and kidney after intravenous
exposure
Barriers and toxicity
Unfortunately, the quantum dot story is not all good news. Their
high heavy metal content makes them extremely toxic to living
creatures. Heavy metals cause developmental abnormalities and
serious health issues, primarily affecting the liver and kidneys.
They cross the blood-brain barrier, accumulate in adipose tissue,
and can remain in the body for up to 10 years. Long exposure to
heavy metals can also lead to carcinogenic effects. In addition, the
excitation process (which causes the fluorescence) results in the
release of destructive reactive and free radical species.
This cytotoxicity remains a barrier to the use of quantum dots in
vivo, but steps have been taken to minimize the toxicity by
modifying the quantum dots with proteins or DNA or adding a
protective coating. One such technique is maltodextrin capping of
quantum dots(2), which has been reported to control toxicity
related to cadmium and selenium leakage and proposed as a
viable option to extend in vivo applications.

21. 21
Addition of maltodextrin-modified
quantum dots to chicken embryos
was found to cause dose-dependent.
Low concentrations of the
maltodextrin quantum dots increased
the rate of cell growth but did not
cause any apparent toxicity. However,
higher concentrations of the
maltodextrin-'protected' quantum
dots, were found to be cytotoxic and
embryotoxic. The most marked
toxicities were in the heart, central
nervous system, neural tube and
somites.
It was also reported that the chorio-
allantoic membrane of the chicken
embryo, which is highly vascularized,
was successfully visualized using
quantum dots.
The quantum dots circulated
unchanged in the embryonic blood
vessels for 4 days.

22. 22
Future perspective of quantum dots
- Future prospective unfolded by quantum dots are in
developing more selective and specific approach of
labelling cells and biomolecules and studying their
interference effects with normal physiology.
- recently developed a novel biomimetic sequence-specific
DNAzyme reaction with cysteine-modified CdTe
nanoparticles under circularly polarized light, which
opens up new applications for QDs as tools in gene
editing for tumor therapy.
- Achieving higher performance and lower toxicity are
urgent requirements for the future development of QDs.
Conclusions and outlook
- QDs have enormous structural and chemical
diversity that can be fine-tuned for application,
thereby making them very attractive materials for
the preparation of composites with enhanced
properties. Particularly, doped QDs have
promoted great development of bioimaging.
- Uncertainty over the toxicity and fate of QDs in
vivo, particularly regarding distribution and
breakdown precludes their use in human
applications until much more data is available.

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