A nanoscale biodegradable polymersome with pH-tuning on-off membrane is prepared via the self-assembly of poly(b-amino ester)-based amphiphilic copolymers. The pH-sensitive polymersome-like vesicle structure includes two layers that can encapsulate either hydrophobic or hydrophilic therapeutic drugs at physiological pH 7.4. Below a pH of 7.0, the polymersome membrane forms tunnels through which the drug cargo can be rapidly released. The size and morphology of the polymersome are measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The pH sensitivity is confirmed by fluorescence spectroscopy. The pH-sensitive drug-delivery polymersome provides a simple and powerful smart carrier for the delivery and controlled release of drugs