Characterization and therapeutic applications of polymersomes

Date

2024-7

Author

Maqsood, Maham

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Cancer is a heterogeneous disease characterized by uncontrolled cell division and growth. New drug delivery systems are being studied and designed for more efficient targeted delivery of drugs in cancer treatment. This thesis investigates the use of polymersomes, self-assembled structures from polymers, as a targeted drug delivery system for cancer treatment. Here, we explore the potential of glucose oxidase (GOx)-loaded polymersomes to induce cytotoxicity in cancer cells. GOx was incorporated into the polymersomes to utilize its enzymatic activity for generating cytotoxic hydrogen peroxide and intending to act as a model enzyme in creating a safe therapeutic delivery system. The study employed triblock copolymers, namely poly(2-isopropyl-2-oxazoline)-b-poly(2-phenyl-2-oxazoline)-b-poly(2-isopropyl-2- oxazoline) (PiPOX-b-PPhOX-b-PiPOX), to fabricate polymersomes using the double emulsion method. Characterization techniques (DLS, TEM, fluorescence imaging, FTIR) revealed size heterogeneity, with aggregates ranging from 200 nm to over 1000 nm. Cell viability assays using SW620 colorectal cancer cells demonstrated good biocompatibility, with both bare and GOx-loaded polymersomes exhibiting minimal cytotoxicity in the medium without glucose. The significant size variation hindered cellular uptake. However, in the presence of a high glucose (4.5 g/L) medium, GOx-loaded polymersomes displayed a significant increase in cell death compared to bare polymersomes, suggesting reactive oxygen species (ROS) mediated cell death via GOx activity. Overall, this study highlights the significant potential of these polymersomes and the opportunity for further optimization. Future research can focus on refining the size distribution, enhancing the loading process, and investigating the cellular uptake mechanisms to boost the therapeutic efficacy of these constructs.

Subject Keywords

Polymersome, Drug Delivery Systems, Colorectal Cancer, Cell Viability, Glucose Oxidase

URI

https://hdl.handle.net/11511/110586

Collections

Graduate School of Natural and Applied Sciences, Thesis