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Application of photoluminescent nanomaterials for diagnosis and therapy of bladder cancer

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thesis
posted on 29.03.2022, 01:46 authored by Dmitry Polikarpov
Approximately three-quarters of bladder cancer patients initially present with a non-muscle invasive tumour, which is usually resected. Transurethral resection can be followed by adjuvant chemo- and immune-therapy. However, in up to 50% of patients, aggressive flat lesions remain intact and progress into muscle-invasive disease, potentially leading to cystectomy and a less favourable outcome. This project addresses the development of novel biohybrid nanocomplexes representing upconversion nanoparticles coupled to antibodies termed targeted upconversion photoluminescent nanoconjugates for photodynamic diagnosis and therapy of bladder cancer. The unique photophysical properties of upconversion nanoparticles allow optical imaging at the centimetre-depth in biological tissue, which is demanded for a number of applications in urology. Coupled to specific antibodies, these nanoconjugates selectively bind to urothelial carcinoma cells and make them visible by emitting visible photoluminescence upon excitation with deeply-penetrating near-infrared light. This photoluminescence can be used for tumour detection and fluorescence-guided resection. In addition, photoluminescent nanoconjugates can carry photosensitiser drugs to cancer cells followed by their photoactivation for targeted photodynamic therapy. In this study, upconversion nanoparticles were synthesised, coated with a silica layer and linked to anti-Glypican-1 antibody MIL38. Incubation with urothelial carcinoma cells with high expression of Glypican-1 (T24) and control cells with low expression of Glypican-1 (C3) demonstrated specific binding of these nanoconjugates to cells expressing the target antigen. This result highlights potential of this technology for further studies of their application in the diagnosis and therapy of bladder cancer.

History

Table of Contents

Chapter 1. Review of current state of bladder cancer and photodynamic diagnosis and therapy -- Chapter 2. Production and charactersiation of targeted upconversion photoluminescent nanoconjugates -- Chapter 3. Culturing and characterisation of urothelial carcinoma cell lines T24 and C3 -- Chapter 4. Trageted labelling of urothelial carcinoma cells by photoluminescent nanoconjugates -- Chapter 5. Discussion, conclusions and future directions -- References.

Notes

Empirical thesis. Bibliography: pages 73-87

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

MRes, Macquarie University, Faculty of Medicine and health Sciences, Department of Clinical Medicine

Department, Centre or School

Department of Clinical Medicine

Year of Award

2016

Principal Supervisor

David Gillatt

Additional Supervisor 1

Andrei Zvyagin

Additional Supervisor 2

Gilles Guillemin

Rights

Copyright Dmitry Polikarpov 2016. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (xiv, 87 pages) colour illustrations

Former Identifiers

mq:69700 http://hdl.handle.net/1959.14/1256888