The　controllable　assembly　of　nanoparticles　significantly　improves　their　biological　effects　in　vivo.　However,　it　is　difficult　to　realize　the　assembly　regulation　of　nanomaterials　under　complex　physiological　conditions.　Herein,　endogenous　glutathione　(GSH)-triggered　vesicles　with　spatiotemporally　confined　aggregation　of　gold　nanogapped　nanoparticles　(AuNNPs)　within　vesicles　were　developed.　These　vesicles　had　excellent　photoacoustic　(PA)　imaging　capability　in　the　near-infrared　second　window　(NIR-II)　for　precise　localization　of　deep　tumors,　measuring　tumor　volume,　and　making　deep　tumors　more　sensitive　to　radiotherapy　and　chemodynamic　therapy　(CDT).　The　vesicles　were　prepared　via　self-assembly　of　MnO2-coated　AuNNPs　that　were　functionalized　by　phosphate-polystyrene　and　bovine　serum　albumin　(AuNNP@MnO2　Ve@BSA).　The　MnO2　shell　was　etched　when　AuNNP@MnO2　Ve@BSA　vesicle　was　exposed　to　GSH,　the　gap　between　intra-vesicular　AuNNP@MnO2　NPs　was　reduced.　This　significantly　enhanced　the　plasmonic　coupling　effect　between　AuNNP@MnO2　NPs,　giving　it　excellent　NIR-II　PA　imaging　capability,　and　thus　can　be　used　to　delineate　the　boundary　and　volume　of　deep-seated　tumors.　Meanwhile,　the　Mn2+-mediated　CDT　released　after　the　etching　of　the　MnO2　shell　interacted　with　GSH-responsive　AuNNP@MnO2　Ve@BSA　and　significantly　inhibited　tumor　growth　due　to　enhanced　radiosensitization　effect.　This　unique　strategy　provides　new　perspectives　and　methods　for　designing　and　applying　biomedical　nanomaterials.　©　2023