Synthetic polymersomes have structure similarity to bio-vesicles and could disassemble in response to stimuli for "on-demand"release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer P(OEGMA-co-EoS)-b-PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and in vivo. This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.