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Although molecular engineering enables precise tuning of molecular structures and properties, it often relies heavily on tedious organic synthesis. Herein, we introduce an intermolecular noncovalent locking strategy to construct systems with optimized photophysical properties for efficient phototheranostics. Aggregation-induced emission luminogens and aggregation-caused quenching luminogens are locked together to construct via multiple noncovalent interactions (e.g., C\u2013H\u00b7\u00b7\u00b7N, C\u2013H\u00b7\u00b7\u00b7S, S\/O\u00b7\u00b7\u00b7N, etc.), suppressing \u03c0\u2013\u03c0 stacking and enhancing fluorescence, while intermolecular charge transfer induces a red-shifted emission and modulates ROS generation pathway. The strong intermolecular noncovalent locks also enforce tight molecular packing, leading to the formation of shuttle-like nanoassemblies rather than conventional nanospheres. Notably, this morphology enables effective tumor accumulation, prolonged retention, and highly efficient phototherapeutic outcome, achieving &amp;gt;90% tumor inhibition with a single injection. The proposed \u201cintermolecular noncovalent locks\u201d approach thus offers a paradigm for the development of advanced phototheranostic agents.<\/jats:p>","DOI":"10.1021\/acsnano.6c08202","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:01:20Z","timestamp":1786006880000},"page":"22838-22850","source":"Crossref","is-referenced-by-count":0,"title":["Intermolecular Noncovalent\nLocks Enable Red-Shifted\nEmission, Modulated Reactive Oxygen Species Generation Pathway, and\nShuttle-Like Nanoassembly for Phototheranostics"],"prefix":"10.1021","volume":"20","author":[{"given":"Zhichao","family":"Gong","sequence":"first","affiliation":[{"name":"Tianjin University , , ,","place":["Tianjin, P. R. 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