Photoallosteric Polymersomes toward On-Demand Drug Delivery and Multimodal Cancer Immunotherapy

Allosteric transitions can modulate the self-assembly and biological function of proteins. It remains, however, tremendously challenging to design synthetic allosteric polymeric assemblies with spatiotemporally switchable hierarchical structures and functionalities. Here, a photoallosteric polymersome is constructed that undergoes a rapid conformational transition from β-sheet to α-helix upon exposure to near-infrared light irradiation. In addition to improving nanoparticle cell penetration and lysosome escape, photoinduced allosteric behavior reconstructs the vesicular membrane structure, which stimulates the release of hydrophilic cytolytic peptide melittin and hydrophobic kinase inhibitor sorafenib. Combining on-demand delivery of multiple therapeutics with phototherapy results in apoptosis and immunogenic death of tumor cells, remold the immune microenvironment and achieve an excellent synergistic anticancer efficacy in vivo without tumor recurrence and metastasis. Such a light-modulated allosteric transition in non-photosensitive polymers provides new insight into the development of smart nanomaterials for biosensing and drug delivery applications.