Architecture-Encoded Degradation Kinetics and Pathways through the Shape and Size of Polymeric Vesicles

Programming the degradation of supramolecular nanostructures is central to their function, clearance, and adaptability, yet prevailing approaches rely primarily on a complex chemical design. How intrinsic physical parameters dictate their degradability remains largely unexplored, limiting general design strategies. Here, we reveal that the architecture of polymeric vesicles, defined by shape and size, encodes both degradation kinetics and disassembly pathways. We demonstrate that a smaller dimension accelerates degradation kinetics. Remarkably, disassembly pathways are dependent on the shape of the self-assemblies: spherical polymersomes collapse globally, whereas stomatocytes undergo a bilayer-resolved stepwise degradation pathway that preserves the inner membrane integrity. These results establish architecture as a primary design principle for programmable biodegradability, uncovering a mechanism by which intrinsic physical properties govern the structural resilience. By connecting shape and size to degradation kinetics and disassembly pathways, our work provides a generalizable framework for engineering nanostructures with spatiotemporally tunable lifetimes, opening new avenues in drug delivery and artificial communication.