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Transition Metal Dichalcogenide (TMDCs) NPs:
Recent Advances in Scientific Research
Presented by
Anju Surendranath
Division of Toxicology
CONTENTS
Section 1
 Introduction
 Examples of TMDCs
 Structure of different TMDCs
 Properties of TMDCs
 Functionalization of TMDCs
 Biomedical applications of TMDCs
 Future advances
 References
Section 2
 Research paper
Transition Metal Dichalcogenides (TMDCs)Transition Metal Dichalcogenides (TMDCs)
Transition Metal Dichalcogenides, which are
sulphides, selenides and tellurides of group 5 and
6 transition elements. Eg: MoS2, ReS2, TaS2, WSe2
etc.,
Formulated as X–M–X, is a plane of transition
metal atoms (M) covalently sandwiched by two
hexagonal planes of chalcogen atoms (X).
Semiconductor materials having tunable
properties.
TMD-based nanomaterials have interesting electro
catalytic and optical properties.
Stability in aqueous environments, large surface area that
can be manipulated and functionalized for biomedical
applications.
Easily be exfoliated using mechanical or chemical
methods. Low levels of toxicity and good biocompatibility
TMDCs have virtually unlimited potential in various
fields, including electronic, optoelectronic, sensing, energy
storage and biomedical applications.
0D, 1D, 2D materials can be easily exfoliated out of
TMDCs.
A potent substitute for carbon based nanoparticles.
EXAMPLES OF TMDCs
Agnieszka et al; Chem. Modell 11.1 (2014)
WS2, MoS2, ReS2, TaS2, WSe2,VS2
etc.,
STRUCTURE OF TMDCs
Agnieszka et al; Chem. Modell 11.1 (2014)
Functionalization of TMDCs
Chen et al; Nanoscale 3.2 (2018)
APPLICATIONS
Zhen et al; ACS nano 11, 2017
Drug Delivery
L.Gong et a.,, Material chemistry (2017)
In vitro Imaging
Jing L et al., Chemical reviews,2016
In vivo imaging
Walling et al, International journal of
molecular sciences (2009)
Cancer therapy
L.Gong et al, Material Chemistry
(2017)
Tissue engineering scaffolds
Jaiswal et al, Advanced Materials (2017)
Future advances
• TMDC nanoparticles and quantum dots for early
diagnosis of diseases.
• Specific therapy without generalized side effects .
• Potent candidate for various biomedical applications
such as bio imaging, molecular diagnosis, drug/gene
delivery, cancer therapy, tissue engineering scaffolds
etc.
• Good photosensitizers for PDT, PTT and
Photoacoustic therapy.
Research paper
Topic:
Directing Assembly and Disassembly of 2D
MoS2 Nanosheets with DNA for drug delivery
Hypothesis
Dox conjugated MoS2nanosheet super structures for
effective and target oriented drug delivery as a
nanomedicine composite.
DNA oligonucleotide and ATP aptamer conjugated
MoS2 nanosheets super structures for effective
Doxorubicin drug delivery by protecting the drug from
in vivo and intracellular degradative enzymes and thereby
specifically targeting the cancer cells.
Aim
Experimental Outline
Synthesis of
MoS2 nanosheets
Thiol group incorporation
on to ss DNA
FAM ATP Aptamer
functionalization
on to ss-DNA
Intracellular Dox
release analysis
Drug loading and
ATP responsive
character analysis
MoS2 NS/ ssDNA/Aptamer
DOX complex
Dox mediated
cell death analysis
Multiple layer
stacking
RESULTS AND DISCUSSION
(a) AFM image and (b Absorption spectrum of the as-obtained MoS2-NS. (c) Absorbance
records (605 nm) of MoS2-NS in ultrapure water and 1× TAE bu er.ff (d) Absorbance
changes of MoS2-NS unmodified P1, disulfide-terminated ssDNA dimer (P1-S−S-P1), and
thiol-terminated ssDNA (P1).
(e) Schematic illustration of DNA functionalization on the dispersity of MoS2-NS.
(f) E ect of the thiol and disulfide group-terminated D1 sequence on the aggregation offf
MoS2-NS.(g) Fluorescence intensity of SYBR Green I with unmodified DNA,
disulphide group incorporated and thiol group incorporated DNA
b
(a) Schematic illustration of drug loading and ATPinduced release of FAM labelled MoS2-NS/ ss DNA
DOX complex. (b) Fluorescence spectra of Dox (4.5 μM) in the absence and presence of D1, MoS2-
NS, and D1/MoS2-NS. (c) Dox loading amount comparison (d) Fluorescence intensities of the Dox-
composite aqueous dispersion after incubation with di erent concentrations of ATP at 37 °C for 1 h.ff
Fluorescent intensity FAM dye released from MoS2 NS surface and
relation with ATP
(e) Fluorescence imaging of MDA-MB-468 cells incubated with Dox/D1 and
Dox/D1/MoS2-NS for 60 min. The nuclei were stained (blue) with Hoechst 33342,
and the ATP aptamer was labeled with FAM fluorophore (green). Scale bar: 10
μm.
(a) Intracellular Dox release analysis after 60 min and 90 min of exposure under ATP rich and ATP poor conditions.
c
(c) Dox release and uptake. Via endolysosomal pathway (d) In vitro cell death analysis using MDA-MB-468 breast
cancer cell lines under ATP rich and ATP poor condition.
(b,b2,c,c2) stacking of multiple layers to form lbl assembly for improved
drug loading and size comparison
e
(d) Avg size comparison for lbl superstructure formation. (e) fluorescence intensity of
DOX diminished when more and more DOX get complexed with the nanosheets
Effect of lbl stacking of multiple MoS2/ DNA/aptamer-DOX for effective tumor size
reduction
Effect of lbl multiple stacking on drug loading efficacy and tumor size
reduction
Conclusion
DNA was first anchored on layered MoS2 nanostructures via the
binding of DNA’s thiol groups to sulfur atom vacancies on MoS2
surfaces.
The duplex/MoS2 NS was considered a base platform, achieving a
high efficacy and autonomous ATP responsive drug delivery.
vertical growth of the DNA/MoS2-NS could be guided by the
targeted aptamer and multilayer MoS2-NS was obtained via LbL
assembly of the thiol-terminated DNA-functionalized MoS2-NS.
This provided more drug loading efficacy for Doxorubicin.
The as-obtained higher-ordered structures formed with the MoS2-
NS as “shields” were highly inert and resistant to the damaging
intracellular DNA degrading enzymes.
The synergetic effects of DNA specificity and 2D plane of MoS2,
a designable stimuli-responsive drug delivery system has been
achieved based on multilayered DNA/MoS2-NS, showing its direct
applicability to the nanomedicine field.
• Aljarb, Areej, et al (2017). "Substrate Lattice-Guided Seed Formation Controls
the Orientation of 2D Transition-Metal Dichalcogenides." ACS nano 11.9 :9215-
9222.
• Kuc, Agnieszka. (2014). "Low-dimensional transition-metal
dichalcogenides." Chem. Modell 11.
• Chen, Hang, et al (2018). "2D transition metal dichalcogenide nanosheets for
photo/thermo-based tumor imaging and therapy." Nanoscale Horizons 3.2;74-89.
• Mouri, S., Miyauchi, Y., & Matsuda, K. (2013). Tunable photoluminescence of
monolayer MoS2 via chemical doping.Nano letters, 13(12), 5944-5948.
• Gong, Linji, et al (2017). "Two-dimensional transition metal dichalcogenide
nanomaterials for combination cancer therapy."Journal of Materials Chemistry
B 5.10 :1873-1895.
• Walling, M. A., Novak, J. A., & Shepard, J. R. (2009). Quantum dots for live cell
and in vivo imaging. International journal of molecular sciences, 10(2), 441-491.
• Jaiswal, Manish K., et al (2017). "Vacancy Driven Gelation Using Defect Rich
Nanoassemblies of 2D Transition Metal Dichalcogenides and Polymeric Binder
for Biomedical Applications." Advanced Materials 29.36:1702037.
REFERENCES
Transition metal dichalcogenide NPs, recent advances in scientific research

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Transition metal dichalcogenide NPs, recent advances in scientific research

  • 1. Transition Metal Dichalcogenide (TMDCs) NPs: Recent Advances in Scientific Research Presented by Anju Surendranath Division of Toxicology
  • 2. CONTENTS Section 1  Introduction  Examples of TMDCs  Structure of different TMDCs  Properties of TMDCs  Functionalization of TMDCs  Biomedical applications of TMDCs  Future advances  References Section 2  Research paper
  • 3. Transition Metal Dichalcogenides (TMDCs)Transition Metal Dichalcogenides (TMDCs) Transition Metal Dichalcogenides, which are sulphides, selenides and tellurides of group 5 and 6 transition elements. Eg: MoS2, ReS2, TaS2, WSe2 etc., Formulated as X–M–X, is a plane of transition metal atoms (M) covalently sandwiched by two hexagonal planes of chalcogen atoms (X). Semiconductor materials having tunable properties. TMD-based nanomaterials have interesting electro catalytic and optical properties.
  • 4. Stability in aqueous environments, large surface area that can be manipulated and functionalized for biomedical applications. Easily be exfoliated using mechanical or chemical methods. Low levels of toxicity and good biocompatibility TMDCs have virtually unlimited potential in various fields, including electronic, optoelectronic, sensing, energy storage and biomedical applications. 0D, 1D, 2D materials can be easily exfoliated out of TMDCs. A potent substitute for carbon based nanoparticles.
  • 5. EXAMPLES OF TMDCs Agnieszka et al; Chem. Modell 11.1 (2014) WS2, MoS2, ReS2, TaS2, WSe2,VS2 etc.,
  • 6. STRUCTURE OF TMDCs Agnieszka et al; Chem. Modell 11.1 (2014)
  • 7. Functionalization of TMDCs Chen et al; Nanoscale 3.2 (2018)
  • 8. APPLICATIONS Zhen et al; ACS nano 11, 2017 Drug Delivery
  • 9. L.Gong et a.,, Material chemistry (2017)
  • 10. In vitro Imaging Jing L et al., Chemical reviews,2016
  • 11. In vivo imaging Walling et al, International journal of molecular sciences (2009)
  • 12.
  • 13. Cancer therapy L.Gong et al, Material Chemistry (2017)
  • 14. Tissue engineering scaffolds Jaiswal et al, Advanced Materials (2017)
  • 15. Future advances • TMDC nanoparticles and quantum dots for early diagnosis of diseases. • Specific therapy without generalized side effects . • Potent candidate for various biomedical applications such as bio imaging, molecular diagnosis, drug/gene delivery, cancer therapy, tissue engineering scaffolds etc. • Good photosensitizers for PDT, PTT and Photoacoustic therapy.
  • 16. Research paper Topic: Directing Assembly and Disassembly of 2D MoS2 Nanosheets with DNA for drug delivery
  • 17.
  • 18. Hypothesis Dox conjugated MoS2nanosheet super structures for effective and target oriented drug delivery as a nanomedicine composite. DNA oligonucleotide and ATP aptamer conjugated MoS2 nanosheets super structures for effective Doxorubicin drug delivery by protecting the drug from in vivo and intracellular degradative enzymes and thereby specifically targeting the cancer cells. Aim
  • 19. Experimental Outline Synthesis of MoS2 nanosheets Thiol group incorporation on to ss DNA FAM ATP Aptamer functionalization on to ss-DNA Intracellular Dox release analysis Drug loading and ATP responsive character analysis MoS2 NS/ ssDNA/Aptamer DOX complex Dox mediated cell death analysis Multiple layer stacking
  • 21. (a) AFM image and (b Absorption spectrum of the as-obtained MoS2-NS. (c) Absorbance records (605 nm) of MoS2-NS in ultrapure water and 1× TAE bu er.ff (d) Absorbance changes of MoS2-NS unmodified P1, disulfide-terminated ssDNA dimer (P1-S−S-P1), and thiol-terminated ssDNA (P1).
  • 22. (e) Schematic illustration of DNA functionalization on the dispersity of MoS2-NS.
  • 23. (f) E ect of the thiol and disulfide group-terminated D1 sequence on the aggregation offf MoS2-NS.(g) Fluorescence intensity of SYBR Green I with unmodified DNA, disulphide group incorporated and thiol group incorporated DNA
  • 24. b (a) Schematic illustration of drug loading and ATPinduced release of FAM labelled MoS2-NS/ ss DNA DOX complex. (b) Fluorescence spectra of Dox (4.5 μM) in the absence and presence of D1, MoS2- NS, and D1/MoS2-NS. (c) Dox loading amount comparison (d) Fluorescence intensities of the Dox- composite aqueous dispersion after incubation with di erent concentrations of ATP at 37 °C for 1 h.ff
  • 25. Fluorescent intensity FAM dye released from MoS2 NS surface and relation with ATP
  • 26. (e) Fluorescence imaging of MDA-MB-468 cells incubated with Dox/D1 and Dox/D1/MoS2-NS for 60 min. The nuclei were stained (blue) with Hoechst 33342, and the ATP aptamer was labeled with FAM fluorophore (green). Scale bar: 10 μm.
  • 27. (a) Intracellular Dox release analysis after 60 min and 90 min of exposure under ATP rich and ATP poor conditions.
  • 28. c (c) Dox release and uptake. Via endolysosomal pathway (d) In vitro cell death analysis using MDA-MB-468 breast cancer cell lines under ATP rich and ATP poor condition.
  • 29. (b,b2,c,c2) stacking of multiple layers to form lbl assembly for improved drug loading and size comparison
  • 30. e (d) Avg size comparison for lbl superstructure formation. (e) fluorescence intensity of DOX diminished when more and more DOX get complexed with the nanosheets
  • 31.
  • 32. Effect of lbl stacking of multiple MoS2/ DNA/aptamer-DOX for effective tumor size reduction
  • 33. Effect of lbl multiple stacking on drug loading efficacy and tumor size reduction
  • 34. Conclusion DNA was first anchored on layered MoS2 nanostructures via the binding of DNA’s thiol groups to sulfur atom vacancies on MoS2 surfaces. The duplex/MoS2 NS was considered a base platform, achieving a high efficacy and autonomous ATP responsive drug delivery. vertical growth of the DNA/MoS2-NS could be guided by the targeted aptamer and multilayer MoS2-NS was obtained via LbL assembly of the thiol-terminated DNA-functionalized MoS2-NS. This provided more drug loading efficacy for Doxorubicin. The as-obtained higher-ordered structures formed with the MoS2- NS as “shields” were highly inert and resistant to the damaging intracellular DNA degrading enzymes. The synergetic effects of DNA specificity and 2D plane of MoS2, a designable stimuli-responsive drug delivery system has been achieved based on multilayered DNA/MoS2-NS, showing its direct applicability to the nanomedicine field.
  • 35. • Aljarb, Areej, et al (2017). "Substrate Lattice-Guided Seed Formation Controls the Orientation of 2D Transition-Metal Dichalcogenides." ACS nano 11.9 :9215- 9222. • Kuc, Agnieszka. (2014). "Low-dimensional transition-metal dichalcogenides." Chem. Modell 11. • Chen, Hang, et al (2018). "2D transition metal dichalcogenide nanosheets for photo/thermo-based tumor imaging and therapy." Nanoscale Horizons 3.2;74-89. • Mouri, S., Miyauchi, Y., & Matsuda, K. (2013). Tunable photoluminescence of monolayer MoS2 via chemical doping.Nano letters, 13(12), 5944-5948. • Gong, Linji, et al (2017). "Two-dimensional transition metal dichalcogenide nanomaterials for combination cancer therapy."Journal of Materials Chemistry B 5.10 :1873-1895. • Walling, M. A., Novak, J. A., & Shepard, J. R. (2009). Quantum dots for live cell and in vivo imaging. International journal of molecular sciences, 10(2), 441-491. • Jaiswal, Manish K., et al (2017). "Vacancy Driven Gelation Using Defect Rich Nanoassemblies of 2D Transition Metal Dichalcogenides and Polymeric Binder for Biomedical Applications." Advanced Materials 29.36:1702037. REFERENCES

Editor's Notes

  1. Non thiolated groups containing DNA strands will not bound to MoS2 ns so after sybr green treatment high fluorescence intensity found where as thiol group incorporated or disulphide group incorporated dna shows no fluorescence as the fluorescence of sybr gren is been quenched due to mos2 incorporation on to thiol and disulphide group oncorporated dna
  2. Schematic illustration of DNA functionalization on the surface of MoS2-NS, indicating that the thiol group is essential for functionalization of MoS2-NS with DNA. Right panel: The influence of DNA hybridization on the dispersity of MoS2-NS in a buffer solution and pictures of MoS2-NS aqueous dispersions in the presence of different kinds of DNA with standing time of 12 h. The thiol-terminated duplex (D1) was obtained via hybridization of the ATP aptamer with P1. (f) Effect of the thiol and disulfide group-terminated D1 sequence on the aggregation of MoS2-NS. Schematic illustration of DNA functionalization on the surface of MoS2-NS, indicating that the thiol group is essential for functionalization of MoS2-NS with DNA. Right panel: The influence of DNA hybridization on the dispersity of MoS2-NS in a buffer solution and pictures of MoS2-NS aqueous dispersions in the presence of different kinds of DNA with standing time of 12 h. The thiol-terminated duplex (D1) was obtained via hybridization of the ATP aptamer with P1. (f) Effect of the thiol and disulfide group-terminated D1 sequence on the aggregation of MoS2-NS. Schematic illustration of DNA functionalization on the surface of MoS2-NS, indicating that the thiol group is essential for functionalization of MoS2-NS with DNA. Right panel: The influence of DNA hybridization on the dispersity of MoS2-NS in a buffer solution and pictures of MoS2-NS aqueous dispersions in the presence of different kinds of DNA with standing time of 12 h. The thiol-terminated duplex (D1) was obtained via hybridization of the ATP aptamer with P1. (f) Effect of the thiol and disulfide group-terminated D1 sequence on the aggregation of MoS2-NS.
  3. Whether thiol group is incorporated on to ss DNA and also to understand whether this DNA is been bound to nanosheets sybr green is used. Decrease of zeta potential of nanosheets from -26 to -35 and -41 after being functionalised with D1 dna and P1 aptamer suggested successful formation of compl;ex
  4. FAM- 5 carboxy fluorescein is a dye incorporated to analyse whether the ATP aptamer is bound to ATP or not. FAM aptamer when bound to DNA willnot emit fluorescence but when it is bound to ATP and get released then the fluorescence intensity get increased. So FAM is used here to confirm the responsiveness of MoS2 ns/DOX/DNA complex.