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We herein resolve these challenges through pioneering a smart \u201cnano\u2010isolation\u201d strategy, synergized with aggregatin\u2010induced emission (AIE)\u2010hemicyanine (Hcy) photosensitizers with an aggregation\u2010gated ROS generation feature. Propelled\u2010type AIE motifs were introduced to planar Hcy derivatives to construct twisted donor\u2010\u03c0\u2010acceptor photosensitizers, among which MTPAON with the largest conformational twist exhibited the best AIE effect and the highest ROS generation, predominantly generating less oxygen\u2010dependent type I ROS. Crucially, MTPAON's ROS generation is gated by aggregation degree, where only tightly packed aggregates activate ROS generation. Leveraging this, we pioneered a \u201cnano\u2010isolation\u201d strategy by encapsulating MTPAON in glutathione (GSH)\u2010responsive nanoparticles at a high polymer ratio (SSPEG\u20107 NPs). This nano\u2010isolation initially suppresses MTPAON's tight aggregation and silences ROS generation. Upon encountering tumor\u2010overexpressed GSH, SSPEG\u20107 NPs disassemble and release MTPAON to form type I ROS\u2010competent aggregates in tumor cells. SSPEG\u20107 NPs thus demonstrated promising antitumor performance under low\u2010dose laser irradiation, while exhibiting negligible off\u2010target phototoxicity to normal tissues. This \u201cnano\u2010isolation\u201d strategy establishes a new paradigm for precision PDT: leveraging stimulus\u2010triggered aggregation to spatially control PDT activation, thereby reconciling the conflict between systemic safety and therapeutic potency.<\/jats:p>","DOI":"10.1002\/adma.73771","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:49:07Z","timestamp":1782233347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Nano\u2010Isolation Strategy for Tumor\u2010Activatable Photodynamic Therapy via Aggregation\u2010Gated Type I Photosensitizers"],"prefix":"10.1002","volume":"38","author":[{"given":"Ping","family":"Liang","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates State Key Laboratory of Luminescent Materials and Devices School of Materials Science and Engineering South China University of 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