A polymer–(multifunctional single-drug) conjugate for combination therapy

Abstract

Combination therapy based on polymer-drug conjugates is one of the exciting developments in polymeric drug delivery systems. A single polymer carrier with two or more drugs attached is advantageous because it provides a platform for synergistic agent action. To expand the concept of combination therapy using a single polymer-drug conjugate, we report a polymer-(multifunctional single-drug) conjugate strategy, in which three different drugs (platinum, azidyl radical and DMC) and two different types of therapies are rationally integrated and then conjugated to an amphiphilic block copolymer. When this polymer-(multifunctional single-drug) conjugate is internalized by cancer cells via endocytosis, the three integrated drugs are expected to be activated and execute therapeutic functions in a sequential fashion under extracellular (UVA irradiation) and intracellular (endosomes/lysosomes) environments to amplify the signals of cancer treatment, especially in cisplatin-resistant cancer cells.