Optimizing enzyme-responsive polymersomes for protein-based therapies - supplementary dataset

<b>Aims: </b>Stimuli-responsive polymersomes are promising tools for protein-based therapies, but require deeper understanding and optimization of their pathology-responsive behavior. <b>Materials &amp; methods: </b>Hyaluronic acid (HA)–poly(b-lactic acid) (PLA) polymersomes self-assembled from block copolymers of varying molecular weights of HA were compared for their physical properties, degradation and intracellular behavior. <b>Results: </b>Major results showed increasing enzyme-responsivity associated with decreasing molecular weight. The major formulation differences were as follows: the HA(5 kDa)–PLA formulation exhibited the most pronounced release of encapsulated proteins, while the HA(7 kDa)–PLA formulation showed the most different release behavior from neutral. <b>Conclusion: </b>We have discovered design rules for HA–PLA polymersomes for protein delivery, with lower molecular weight leading to higher encapsulation efficiency, greater release and greater intracellular uptake.