Application of photoluminescent nanomaterials for diagnosis and therapy of bladder cancer
thesisposted on 2022-03-29, 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.