Biomedical applications of quantum dots
- 1. Anju Surendranath Toxicology Division Biomedical Applications of Quantum Dots
- 2. CONTENTS Introduction Photo-physical properties of QDs Comparison of fluorescence between dye and QDs Biomedical applications Future Advances References Research Paper
- 6. • Small in size • Broad absorption spectra & size tunable narrow emission spectra • Enormous absorption extinction coefficients • High fluorescent quantum yields. • Photo chemically robust. • Resistant to photo bleaching. • Shows fluorescence intermittency. PHOTOPHYSICAL PROPERTIES OF QDs
- 7. Comparison between fluorescence properties of QDs and organic dyes PROPERTIES DYES QDs Absorption spectra Discrete bands Broad bands Emission spectra Asymmetric Symmetric, Gaussian profile Quantum yield 0.5-1(visible),0.05- 0.25(NIR) 0.1-0.8(visible), 0.2- 0.7(NIR) Molar absorption coefficient 2.5×10 4 -2.5 ×10 5 M-1 cm-1 105-106M-1 cm-1 Fluorescence life times 1-10 ns 10-100 ns Size ˜0.5 nm; Molecule 1-10 nm Toxicity From very low to high(depend on dye) Heavy metal leaching causes toxicity Stocks shift Normally <50 nm upto >150 nm Typically <50 nm for visible wavelength emitting QDs. Solubility/Dispersibility Control by substitution pattern Control via surface chemistry
- 9. Biomedical Applications In vitro imaging In vivo imaging Other applications SLN biopsy Live cell imaging Fixed cell imaging Biosensing Cancer studies PTT, PDT, PAT Gene Delivery Drug delivery Tracking of membrane receptors and signalling pathways Phago-kinetic assays Resonance Energy Transfer FRET, BRET Stem cell tracking Immuno fluorescent labelling of proteins Immuno histochemistry detection FISH
- 11. DETECTION OF TARGET ANALYTE
- 12. FLUORESCENT IMAGING USING QDs • QDs as labels in biological research first reported by Alivisatos and Nie in 1998. Successfully used as fluorescent labels for a variety of bioanalytical purposes such as Detection of DNA, Proteins and other biomolecules. Cellular labelling Binding assays (FRET) • Imaging mainly two type In vitro imaging In vivo imaging
- 14. Quantum Dots Based Nanoplatform for Brain Imaging Shao, et al, Nanoscale (2016)
- 15. Imaging Guided Therapy based on QDs Imaging Guided Therapy based on QDs
- 16. PATHOGEN AND TOXIN DETECTION Mohamadi et al; Journal of Photochemistry and Photobiology B: Biology (2017)
- 17. Mei et al; 2016, Nanoscale Research Letters QDs for targeted drug delivery
- 18. Mei et al; 2016, Nanoscale Research Letters
- 19. GENE TECHNOLOGY QD-based DNA nanosensors T. Jamieson et al. Biomaterials 28 (2007)
- 20. QDs in photodynamic therapy Jiang et al, Nanoscale (2013)
- 22. FLOURESCENCE IN SITU HYBRIDIZATION Control (no QD conjugate) Streptavidin QD 605 detection of chromosome 1q12 region in homologous chromosomes (vertical and horizontal arrows) Sarwat B. Rizvi et al Nano Reviews 2010.
- 23. FUTURE ADVANCES • 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, imaging based therapies etc;. • Good photosensitizers for PDT, PTT and Photoacoustic therapy.
- 24. • RESEARCH PAPER Title: MoS2 @ polyaniline nanohybrids for in vivo dual model imaging guided synergistic photothermal/radiation therapy
- 26. Hypothesis Nanoscaled transition metal dichalcogenide MoS2 quantum dot@polyaniline (MoS2@PANI) nanohybrids to be used as both photothermal adsorbing agents and radiosensitizers for combined PTT and RT
- 27. Aim • Tumor is associated with hypoxic condition which will create radiation resistance (A curse to radiotherapy) • Development of MoS2@PANI nanohybrids could improve photothermal therapy (PTT) efficiency. • This PTT can reduce tumor hypoxia through appropriate hyperthermia. • Thus a combined PTT/RT using MoS2@PANI could effectively make tumor size reduction in vivo.
- 28. (a) Synthetic process diagram of MoS2@PANI nanohybrids.
- 29. (b) TEM image of MoS2 QDs. (c) TEM image of MoS2@PANI nanohybrids. (d) Size distribution of MoS2 QDs and MoS2@PANI nanohybrids. (e) Fluorescence spectra of MoS2@PANI nanohybrids. (f) UV−vis−NIR absorbance spectra of MoS2 QDs and MoS2@PANI. (g) The temperature and photothermal images of pure water, MoS2 QDs, pure PANI, and MoS2@PANI nanohybrids (0.1 mg mL−1) solutions as a function of 808 nm laser irradiation time at the power intensity of 1.5 Wcm−2.
- 30. (a) Cell viabilities of 4T1 cells treated with PBS, MoS2, or MoS2@PANI with or without laser irradiation (808 nm, 1.5 W cm−2) and X-ray radiation (6 Gy). (b) Live−dead staining images of 4T1 cells treated with PBS, MoS2@PANI + PTT, MoS2@PANI + RT, MoS2@PANI + PTT + RT, respectively. The nanoparticle concentration was 0.1 mg mL−1
- 31. (c) Fluorescence images of 4T1 cells incubated with MoS2 QDs, MoS2@PANI nanohybrids, and MoS2@PANI nanohybrids under 808 nm NIR irradiation. (d) Representative fluorescence images of DNA fragmentation and nuclear condensation induced by PBS or MoS2@PANI nanohybrids with/ without 808 nm laser irradiation, stained with DAPI and γ-H2AX for nuclear visualization and DNA fragmentation, respectively.
- 32. (a) Scheme of MoS2@PANI nanohybrids used for dual modal imaging and combined PTT and RT. (b) Ultrasound (US) images and PA images of 4T1 tumors after intravenously injected with MoS2@PANI nanohybrids at different time points. (c) In vivo CT images of 4T1 tumor-bearing mice before and 8 h after intravenous injection with MoS2@PANI nanohybrids. (d) In vivo CT images of tumors on mice before and 8 h after iv injection
- 33. (e) Corresponding intensity of the photoacoustic signal of MoS2@PANI nanohybrids in the tumor at different time points. (f) Corresponding HU value of MoS2@PANI nanohybrids in the tumor before injection and 8 h after injection.
- 34. (a) Photothermal images of 4T1 tumor-bearing mice under the 808 nm laser irradiation (1.5 W cm−2, 5 min) after administration of PBS, MoS2 QDs and MoS2@PANI nanohybrids, respectively. (b) Tumor growth in different groups of mice after various treatments.
- 35. (c) Representative immunofluorescence images of tumor slices. The nuclei, blood vessels, and hypoxic areas were stained with DAPI (blue), anti-CD31 antibody (red) and antipimonidazole antibody (green), respectively. (d) Quantification of hypoxia areas in the tumors from different groups’ mice. (e) Histopathological analysis of various tissue sections.
- 36. Conclusion • MoS2@PANI nanohybrids demonstrated good compatibility in physiological environments and excellent biocompatibility in both in vitro and in vivo studies. • Exhibits strong X-ray attenuation and high NIR absorption efficiency which can be used for dual-modal CT and PA imaging. • Bimodal CT/PA images demonstrated the efficient tumor accumulation of these nanohybrids after systemic administration into tumor-bearing mice. • A remarkable synergistic cancer treatment effect was observed using this nanomaterial based PTT/RT combination therapy .
- 37. REFERENCES • Singh, S., Chakraborty, A., Singh, V., Molla, A., Hussain, S., Singh, M. K., & Das, P. (2015). DNA mediated assembly of quantum dot–protoporphyrin IX FRET probes and the effect of FRET efficiency on ROS generation. Physical Chemistry Chemical Physics, 17(8), 5973-5981. • Zhao, M. X., & Zhu, B. J. (2016). The research and applications of quantum dots as nano-carriers for targeted drug delivery and cancer therapy. Nanoscale research letters, 11(1), 207. • Jamieson, T., Bakhshi, R., Petrova, D., Pocock, R., Imani, M., & Seifalian, A. M. (2007). Biological applications of quantum dots. Biomaterials, 28(31), 4717-4732. • Mohamadi, E., Moghaddasi, M., Farahbakhsh, A., & Kazemi, A. (2017). A quantum-dot-based fluoroassay for detection of food-borne pathogens. Journal of Photochemistry and Photobiology B: Biology, 174, 291-297. • Rizvi, S. B., Ghaderi, S., Keshtgar, M., & Seifalian, A. M. (2010). Semiconductor quantum dots as fluorescent probes for in vitro and in vivo bio-molecular and cellular imaging. Nano reviews, 1(1), 5161. • Jiang, Shan, et al. "Surface-functionalized nanoparticles for biosensing and imaging-guided therapeutics." Nanoscale 5.8 (2013): 3127-3148.