Toward enzyme-responsive polymersome drug delivery

In drug delivery, enzyme-responsive drug carriers are becoming increasingly relevant because of the growing association of disease pathology with enzyme overexpression. Polymersomes are of interest to such applications because of their tunable properties. While polymersomes open up a wide range of chemical and physical properties to explore, they also present a challenge in developing generalized rules for the synthesis of novel systems. Motivated by this issue, in this perspective, we summarize the existing knowledge on enzyme-responsive polymersomes and outline the main design choices. Then, we propose heuristics to guide the design of novel systems. Finally, we discuss the potential of an integrated approach using computer simulations and experimental studies to streamline this design process and close the existing knowledge gaps. Tweetable abstract: How can we optimize the design of enzyme-responsive polymersomes to better treat disease? In this perspective, three common modes of enzymatic action in these nanoparticles are identified.