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Uncontrolled \u201calways\u2010on\u201d catalysis or irreversible activation prevents timely termination, making it difficult to confine prodrug activation within a safe therapeutic window. To address this challenge, we developed an ultrasound\u2010recharging\u2010regulated closed\u2010loop bioorthogonal system integrating on\u2010demand activation, enhanced catalytic performance, and self\u2010termination, enabling precise in vivo prodrug activation. Mechanistically, pyroelectric polarization of BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    induces deposition of sub\u2010nanometer Pd clusters whose catalysis is initially silenced by rapid oxidative passivation. Upon ultrasound stimulation, the piezoelectric BaTiO\n                    <jats:sub>3<\/jats:sub>\n                    core generates a built\u2010in electric field that reduces surface Pd\n                    <jats:sup>2+<\/jats:sup>\n                    to catalytically active Pd\n                    <jats:sup>0<\/jats:sup>\n                    , thereby activating bioorthogonal reactions while promoting charge separation and reactive oxygen species generation. Simultaneously, piezoelectric screening charges accelerate interfacial electron transfer, significantly enhancing catalytic kinetics. Crucially, rapid repassivation after ultrasound cessation leads to complete catalytic deactivation, establishing a closed bioorthogonal cycle following a single stimulus. In vitro and in vivo studies demonstrate that the activated species induce immunogenic cell death while avoiding side effects from persistent catalysis. This work presents a safe, controllable, and efficient paradigm for bioorthogonal catalytic therapy, advancing its clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/advs.76338","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:15:22Z","timestamp":1782915322000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ultrasound\u2010Recharged Sub\u2010Nanometer Palladium Catalysts for on\u2010Demand and Self\u2010Terminating Bioorthogonal Prodrug Activation in Cancer Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Daqing","family":"Xia","sequence":"first","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology College of Bioengineering Ministry of Education Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key 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Pharmacy The Second Affiliated Hospital Army Medical University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3460-0867","authenticated-orcid":false,"given":"Jixi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology College of Bioengineering Ministry of Education Chongqing University  Chongqing 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