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Our previous studies established that nanodiamonds (NDs) function as nanoparticle autophagy inhibitors (NAPIs) when delivered systemically, markedly enhancing ATO efficacy in orthotopic liver tumour models by blocking NUPR1\u2010mediated autolysosomal clearance. However, systemic administration remains inefficient in modulating the local autophagic microenvironment within tumours. Here we developed an interventional strategy based on intratumoral injection to assess the feasibility and biosafety of locally blocking autophagic flux while substantially reducing the required ATO dosage, thereby maximising the synergistic anti\u2010tumour effects of NDs and ATO. In HepG2 hepatocellular carcinoma cells, NDs markedly blocked the late stage of autophagic flux, thereby significantly amplifying ATO\u2010induced apoptosis. In a subcutaneous xenograft liver cancer mouse model, intratumoral co\u2010administration of NDs with low\u2010dose ATO achieved ~91% tumour inhibition and effectively eliminated the systemic toxicity associated with high\u2010dose ATO monotherapy. Notably, the synergistic antitumor effect was independent of increased intratumoral ATO accumulation and was driven instead by targeted modulation of the autophagic pathway. Collectively, this study demonstrates a mechanism of localised, nanomaterial\u2010mediated autophagy regulation and offers an efficient, safe strategy for interventional therapy of advanced solid tumours.<\/jats:p>","DOI":"10.1111\/cpr.70234","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:56:14Z","timestamp":1779198974000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Localised Autophagy Inhibition by Nanodiamonds Potentiates Arsenic Therapy With Favourable Safety Profile in Solid Tumours"],"prefix":"10.1111","volume":"59","author":[{"given":"Yiliu","family":"Wang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences  Shanghai China"},{"name":"Institute of Materiobiology, College of Sciences Shanghai University  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifen","family":"Cui","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jichao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shitai","family":"Zhu","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences  Shanghai China"},{"name":"Institute of Materiobiology, College of Sciences Shanghai University  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linjie","family":"Guo","sequence":"additional","affiliation":[{"name":"Institute of Materiobiology, College of Sciences Shanghai University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qisheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Materiobiology, College of Sciences Shanghai University  Shanghai China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Traumatology, Rui Jin Hospital, School of Medicine Shanghai Jiao Tong University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4971-9103","authenticated-orcid":false,"given":"Huating","family":"Kong","sequence":"additional","affiliation":[{"name":"Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-022-04463-7"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117093"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-0054"},{"issue":"9","key":"e_1_2_10_5_1","first-page":"3345","article-title":"Use of Arsenic Trioxide (As2O3) in the Treatment of Acute Promyelocytic Leukemia (APL).1. 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