Clickable biocompatible brush polymers as a versatile platform toward development of multifunctional drug delivery vehicles

Abstract

Clickable polymers have been gaining attention in the biomedical field because of their ability to carry various functional moieties, including drugs, imaging agents, and cell targeting ligands made by highly efficient click-reaction chemistry. In particular, brush polymers formed by the conjugation of polyethylene glycol (PEG) to clickable polymers are very promising for developing advanced drug delivery systems because of the enhanced water-solubility, biocompatibility, and so-called “stealth” capabilities. Recently, we developed and patented a clickable brush polymer PEAMO-g-PEG by the ring-opening polymerization of an alkyne-substituted oxetane monomer following the conjugation of PEG via Cu(I)-catalyzed azide-alkyne cycloaddition click reaction. The clickable brush polymer has excellent water solubility and biocompatibility as well as flexibility for coupling therapeutic drugs and other multi-modality entities. A novel chronotherapeutic polymeric drug for brain cancer therapy was then developed using the brush polymer platform as an example of this technology. The anticancer drug camptothecin primarily targeting proliferating cells was coupled to the PEAMO polymer and delivered to mouse brain via intra-tumoral delivery resulting in significantly improved survival. In this perspective, we review and discuss this new drug delivery platform with an in-depth discussion of its structural features, properties, and therapeutic applications. Future directions and possible utilization of this platform for novel formulations are also elaborated upon.