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Published byPreston McDowell Modified over 6 years ago
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Novel Polyglutamate-based Indocyanine green nanoparticles for photothermal cancer therapy
Sam P. Tarassoli
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Clinical need: head and neck cancer
Cancer cost: £9.4 billion to the NHS 37% spent on effective treatment Need for more direct and targeted therapy Head and neck cancer prognosis is good (50% 5y sr) with 6th leading incidence rate Aim To create a Polyglutamic acid-Indocyanine green polymeric nanoparticle that can improve the delivery of saporin to a head and neck cancer cell Cell line SCC-9
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Nanoparticles for drug delivery
Internal stimuli sensitive nanoparticles Photothermal therapy and photothermal internalising effect Internal stimulus: Overexpressed tumour enzymes tumour agent polymer cleaved by cathepsins cathepsin enzymes
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PGA digestion with cathepsin B
Fainter bands = PGA digestion over time
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NP characterisation SEM DLS Encapsulation efficiency = 0.85 +/- 0.06%
Zeta potential = /- 1.3 mv (n=3)
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Absorbance and fluorescence spectra
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ICG uptake and formulation
LASER: 805nm and 150mW/cm2 for 5 mins (45 J/cm2 total energy)
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Saporin toxicity studies
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Rhodamine Dextran tracking microscopy
LASER TREATED
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Further work SEM for digested nanoparticle
Challenging to create sample where buffer has been completely removed to provide a clear image Fabrication of nanoparticle that contains polymer photosensitizer chemotherapeutic Figure out a method to measure photothermal effect of the nanoparticle within the internal environment of the cell Cytotoxicity depends on ICG sequestration
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Conclusions Incorporation of ICG in the PGA-based nanoparticles significantly increased the light-induced cytotoxicity of the agent on SCC-9 cells Primarily a result of the improved cellular uptake of the NP formulation Cytotoxicity evaluation and intracellular distribution observations suggested a synergistic effect of NIR-triggered drug release from lysosomes in the presence of ICG-containing nanoparticles
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Acknowledgements University College London
Division of Surgery and Interventional Science Dr Nikoleta Nomikou Dr Josephine Woodhams Halla Weinhert Division of Chemistry UCL Cancer Institute Ulster University, School of Pharmacy
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Thank you for listening!
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Accompanying slides
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Free ICG and PGA-ICG fluorescence and absorbance profiles
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NP digestion analysis by membrane size
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