Delivery system designs for platinum prodrug in cancer treatment

• Main Author: Lim, Wei Qi
• Other Authors: Zhao Yanli
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: Engineering::Nanotechnology
• Online Access: https://hdl.handle.net/10356/104277; http://hdl.handle.net/10220/50274
• Institution: Nanyang Technological University

Platinum-based drugs are among the most powerful and widely used chemotherapy drugs. However, it is challenging to selectively deliver and accumulate these drugs in the targeted pathological regions to avoid off-target toxicity to healthy tissues. Recently, developing novel platinum prodrugs to overcome the challenges and facilitate tumor-activated cytotoxicity has been a favored strategy. To further enhance selectivity, delivering the drugs in nanostructures rather than their molecular forms takes advantage of the enhanced permeability and retention effect for selective tumor accumulation and improves pharmacokinetics. Therefore, there is an increasing attention on exploring the construction of platinum prodrug-based nanoparticles for effective cancer treatment. Adapting the natural phenomena of amphiphilic self-assembly, this dissertation highlights the different approaches to fabricate platinum(IV) prodrug self-assembled delivery systems and its combination with other therapeutic agents to enhance treatment efficacy in vitro and in vivo. To achieve site targeting and controlled drug release, active targeting ligand moiety was conjugated to a platinum(IV) prodrug scaffold which subsequently formed amphiphilic self-assembled nanoparticles. Furthermore, capitalizing on the synergistic effects of combination therapy, supramolecular self-assembled nanoconjugates comprising oxaliplatin prodrugs and therapeutic agents such as photosensitizers and cytotoxic proteins were rationally designed to maximize treatment efficacy. Using nanotechnology and the elegance of self-assembly, these proposed delivery systems investigated in this dissertation provides an inspiring outlook for use of platinum(IV) prodrug-based nanocarrier in cancer therapy.