Balloon-like polymersomes with tunable charged and burstable interfaces for controlled drug delivery

Inherent instability, low response efficiency, and lack of functionality have hindered the clinical application of polymer drug carriers. Addressing these challenges through straightforward molecular design remains a significant obstacle. Here, we introduce a novel approach using a structurally simple, clickable amphiphilic diblock copolymer vesicle. Our strategy involves asymmetric functionalized interfacial crosslinking, which modifies the interfacial curvature to induce polymersome swelling and stabilizes this metastable state through a disulfide-bond-crosslinked network, reminiscent of an inflated balloon. Moreover, the side chain functional groups of the crosslinking agent provide the self-assembled structures with controllable and switchable surface charges. This feature allows for the manipulation of nanoparticle internalization pathways, tissue distribution and tumor targeting efficacy in vivo. Notably, these functionalized balloon-like polymersomes can burst rapidly under the stimulation of glutathione, thereby facilitating efficient and specific intracellular drug release. This study presents an effective solution to the longstanding dilemma of stability, release, and functionality in diblock copolymer carriers, paving the way for the development of intelligent drug carriers with significant clinical translation potential.