Chitosan nanoparticles with encapsulated Rose Bengal for photodynamic treatment of human prostate and breast cancer cells

Abstract

Cancer remains a significant global health challenge due to the limitations of current treatment options, including off-target toxicity, resistance, and limited efficacy. Photodynamic therapy offers a promising approach to treating cancer by using photosensitisers and specific light wavelengths to selectively destroy cancerous cells while leaving healthy cells relatively unharmed. However, the hydrophilic nature of some photosensitisers, such as Rose Bengal, limits their clinical use. To overcome these limitations, various nanocarriers have been developed to deliver RB inside the tumour microenvironment, and chitosan nanoparticles have emerged as promising candidates due to their high biocompatibility and biodegradability. The thesis presents a simple fabrication protocol for producing RB-encapsulated chitosan nanoparticles with a peak particle size of ∼200 nm. The purification protocol for nanoparticles (NPs) resulted in a narrower size distribution, ranging from 200 to 300 nm, making them suitable for immediate use in biomedical applications, including photodynamic therapy. The thesis also describes the characterisation of the RB-encapsulated chitosan nanoparticles, including their size, shape, morphology, and hydrodynamic diameter, using scanning electron microscopy, dynamic light scattering, and atomic force microscopy. Furthermore, the thesis investigated the efficacy of these NPs in killing cultured human breast cancer cells (MCF-7 and MDA-MB-231) and prostate cancer cells (PC3) in vitro. The RB-encapsulated nanoparticles generated more reactive oxygen species compared to NPs without RB and RB alone in a dose-dependent manner. They killed 94%-98% of cultured human breast and prostate cancer cells with different dosage regimens. Overall, this thesis demonstrates the potential of RB-loaded chitosan nanoparticles as a promising strategy for anticancer PDT in preclinical and clinical settings by overcoming the limitations of RB's hydrophilic nature and short half-life (Half-life refers to the time it takes for half of a substance to decay or be eliminated from the body, while a short half-life indicates that the substance's concentration or activity decreases quickly over a short period). The simple fabrication protocol for chitosan nanoparticles and the efficient protocol for characterising and purifying NPs for biomedical applications provide a foundation for future research in this field.

Date of Award	2023
Original language	English
Awarding Institution	Western Sydney University
Supervisor	Antonio Lauto (Supervisor)