Nano Trojan Horse: A polymeric drug delivery system for platinum chemotherapeutics

Abstract

The object of this thesis is to synthesis new for the delivery of platinum chemotherapeutics. Water soluble block copolymers were initially synthesised using oligo(ethylene glycol) methylether methacrylate (OEGMEMA) and methacrylic acid (MAA) and upon the attachment of platinum (IV) complex (Oxoplatin) the polymer becomes amphiphilic and self assembles into micelle structure in aqueous environment. The surfaces of these macromolecular micelles are decorated with folic acid for enhanced tumour targeting ability and are internalised via specific cellular uptake pathway – receptor mediated endocytosis (RME). The attachment of folate is achieved via the R-group modification of the RAFT agent used in polymerisation resulting in polymers to terminate with a dopamine functionalised end group. The attachment between folate and the terminals of the polymer exist in a reversible boronate ester group and its binding conditions have been investigated in this thesis. The in vitro studies show a promising antitumor activity from the platinum (IV) incorporated micellar delivery system and that the cytotoxicity can be enhanced by stabilising the micelle structure via crosslinking and the attachment of folate on the surface for pathway specific endocytosis. The cytotoxic properties of platinum incorporated micelles can also be increased by utilising a dual drug system with curcumin which has also been explored in this thesis.