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In tumor tissues, RGLS cooperated with OXA to intensify mitochondrial dysfunction and excessive mitophagy, leading to increased tumor cell death and amplified immunogenic cell death, as indicated by enhanced calreticulin exposure and HMGB1 release. This immunogenic remodeling promoted dendritic cell maturation, increased intratumoral infiltration of CD4+ and CD8+ T cells, and attenuated OXA-induced PD-L1 upregulation, collectively converting immune-cold tumors into immune-hot phenotypes. In contrast, in dorsal root ganglia, RGLS restored OXA-impaired PINK1\/Parkin-dependent mitochondrial quality control, reduced mitochondrial reactive oxygen species accumulation, and protected neurons from chemotherapy-induced injury, thereby alleviating peripheral neuropathy. These findings establish sporoderm removal as a biointerface-modulation strategy for transforming Ganoderma lucidum spores into multifunctional therapeutic particles and highlight RGLS as a promising adjuvant platform to improve the therapeutic index of OXA-based colorectal cancer chemotherapy.<\/jats:p>","DOI":"10.1021\/acsami.6c14400","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:01:31Z","timestamp":1792580491000},"source":"Crossref","is-referenced-by-count":0,"title":["Sporoderm-Removed Particles Enhance Oxaliplatin Immunochemotherapy against Colorectal Cancer and Mitigate Neurotoxicity via Dual-Directional PINK1\/Parkin Mitophagy"],"prefix":"10.1021","author":[{"given":"Wei","family":"Yan","sequence":"first","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]},{"name":"Shandong First Medical University ,","place":["Jinan, China, 250117"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Jin","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Shao","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0642-9155","authenticated-orcid":true,"given":"Guoyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Ma","sequence":"additional","affiliation":[{"name":"Chinese Academy of Sciences , , ,","place":["Beijing, China, 100190"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenhao","family":"Li","sequence":"additional","affiliation":[{"name":"Shouxiangu Botanical Drug Institute , ,","place":["Hangzhou, China, 311100"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanghui","family":"Zhu","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manman","family":"Xu","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0952-093X","authenticated-orcid":true,"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Guang\u2019anmen Hospital, China Academy of Chinese Medical Sciences , ,","place":["Beijing, China, 100053"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"issue":"3","key":"2026102107012468500_cit1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA: Cancer J. 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