Systemic administration of chemotherapeutics is associated with various side effects deriving from accumulation in off-target sites and acute toxicity of the drugs. In the past decade, engineering targeted drug delivery platforms arose as a novel paradigm to overcome such obstacles and ultimately achieve advanced forms of chemotherapy.

This thesis reports successful syntheses of l-RSP, a redox-sensitive self-immolative polymer, and DNS-SN38, thiol-sensitive SN-38 prodrug, as potential candidates for targeted drug delivery platforms.

By covalently conjugating a redox-trigger (p-nitrobenzyl alcohol) and self-immolative linker (p-hydroxybenzyl alcohol) to the cyclization spacer (n-2-(hydroxyethyl)ethylene diamine), a novel self-immolative monomer was obtained. Polymerization of the respective monomer yielded a linear redox-sensitive polymer (l-RSP) that is capable of systemic degradation via sequential 1,6-elimination and 1,5-cyclization reactions upon redox-stimulus. Ultimately, the polymer's potential for biomedical application was simulated through in vitro redox-triggered release of paclitaxel from polymeric nanoparticles.

SN-38 (7-ethyl-10-hydroxy-camptothecin), a potent metabolite of irinotecan (CPT-11), has been extensively investigated in the past for direct usage in order to fully exploit its cytotoxic potency. Here, 2,4-dinitrobenzene sulfonyl (DNS) moiety was conjugated to SN-38 to furnish a thiol-sensitive prodrug, denoted as DNS-SN38, that can be activated in the intracellular regions with GSH abundance. Furthermore, due to strong electron-withdrawing potential of DNS, the inherent fluorescence of SN-38 could be virtually quenched with intact conjugation. By investigating the prodrug's activation property upon thiol-sensitive trigger cleavage via fluorescence activation and cytotoxicity against A2780 and mCherry+OCSC1-F2 cell lines, its vast potential as a viable theranostic agent was demonstrated.