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In the content, we constructed a cascade\u2010responsive nanoplatform based on porous hollow gold nanocages (GNCs) that integrates spatial targeting and temporal activation of multimodal treatment. By co\u2010loading the near\u2010infrared (NIR) photosensitizer indocyanine green (ICG) and the NO precursor L\u2010Arg into GNCs, and conjugating the HCC\u2010targeting peptide 9R\u2010P201 on the surface, we obtained the multifunctional nanoplatform GIL9R. Upon NIR irradiation, GIL9R nanoplatform simultaneously generated localized hyperthermia (photothermal therapy, PTT) and the resulting strong oxidizing agent. The resulting reactive oxygen species (ROS) catalyze L\u2010Arg oxidation via an enzyme\u2010mimetic pathway to produce NO, triggering gas therapy (GT) in situ. This PTT\/PDT\u2010initiated NO release synchronizes three modalities, yielding potent synergistic cytotoxicity against HCC cells. In vitro, GIL9R nanoplatform showed high HCC affinity, effective photodynamic therapy (PDT), and robust NO\u2010mediated GT. In vivo, GIL9R nanoplatform selectively accumulated in tumors and significantly suppressed tumor growth. This rationally designed cascade platform leverages intrinsic synergy among PTT, PDT, and GT, offering a translatable strategy for precision liver cancer treatment.<\/jats:p>","DOI":"10.1002\/smll.73927","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:25:59Z","timestamp":1779791159000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Photothermally Triggered Cascade Nanodelivery Platform for On\u2010Demand Nitric Oxide Release in Targeted Hepatocellular Carcinoma Therapy"],"prefix":"10.1002","volume":"22","author":[{"given":"Bang\u2010Bang","family":"Liu","sequence":"first","affiliation":[{"name":"Henan Key Laboratory of Natural Medicine Innovation and Transformation Henan University  Kaifeng China"},{"name":"State Key Laboratory of Antiviral Drugs Henan University  Kaifeng 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