Microparticle templating as a route to nanoscale polymer vesicles with controlled size distribution for anticancer drug delivery

Abstract Polymer vesicles are self-assembled shells of amphiphilic block copolymers (BCPs) that have attracted tremendous interest due to their encapsulation ability and intracellular delivery of therapeutic agents. However, typical processes for the formation of polymer vesicles lead to ensembles of structures with a broad size distribution (from nanometer to micrometer scale) which result in a limitation for efficient cellular uptake. In this study, we present a simple and efficient approach for the fabrication of polymer vesicles with uniform nanoscale dimensions from template formation of electrosprayed particles in a high throughput manner. First, electrospraying was applied to produce micrometer-sized templates of a block copolymer before polymer vesicles were formed from the pre-prepared microparticles via rehydration. Four different biocompatible diblock and triblock copolymers were used to successfully fabricate polymer vesicles with uniform size around 150 nm using this approach. Furthermore, we encapsulate anticancer drug doxorubicin (DOX) within the polymer vesicles via this method. The kinetics of cellular uptake (HeLa cell) and intracellular distribution of DOX-loaded polymer vesicles have been quntified and monitored by flow cytometry and confocal microscopy, respectively. The results show that our new method provides a promising way to fabricate drug-loaded polymer vesicles with controllable nanoscale size for intracellular anticancer drug delivery.