{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:10:31Z","timestamp":1788869431227,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) remains therapeutically challenging due to high metastasis, recurrence, and immunotherapy resistance driven by tumor microenvironment\u2010mediated immune evasion. Immunogenic cell death (ICD) offers a promising strategy to reshape the immune microenvironment, yet existing ICD inducers suffer from poor targeting efficiency and insufficient death signal release. Here, we constructed a calcium overload\u2010based smart nanosystem, HA\u2010HAP@CUR, to achieve highly efficient ICD induction via a triple\u2010effect mechanism: hyaluronic acid (HA)\u2010mediated CD44 targeting enables tumor\u2010selective accumulation; pH\u2010responsive hydroxyapatite (HAP) degradation releases Ca\n                    <jats:sup>2+<\/jats:sup>\n                    in the acidic tumor microenvironment; and curcumin (CUR) amplifies intracellular calcium overload by promoting endoplasmic reticulum Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release, collectively establishing a positive feedback loop disrupting calcium homeostasis. Mechanistically, calcium overload induces mitochondrial membrane potential dissipation and sustained mPTP opening, triggering mitochondrial oxidative stress and energy metabolic disorders. This mitochondrial crisis concurrently activates caspase\u20103, GSDMD, and RIPK1, synergistically initiating apoptosis, pyroptosis, and necroptosis, ultimately converging into PANoptosis with potent immunostimulatory potential. This strategy, encompassing targeted accumulation, calcium storm activation, and multi\u2010modal cell death synergy, provides a biologically precise approach to overcoming immunotherapy resistance in CRC.\n                  <\/jats:p>","DOI":"10.1002\/advs.75559","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:14:56Z","timestamp":1778066096000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CD44\u2010Targeting Hydroxyapatite Nanoparticles (HAP) Induce Mitochondrial Dysfunction\u2010Driven PANoptosis and Immunogenic Cell Death (ICD) via Ca Overload in Colorectal Cancer"],"prefix":"10.1002","volume":"13","author":[{"given":"Yao","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haosen","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of General Surgery Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and Science  Xiangyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine Key Laboratory of Biological Targeting Diagnosis Therapy and Rehabilitation of Guangdong Higher Education Institutes The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"},{"name":"The Fifth Clinical College of Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qunfeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery Affiliated Hospital of Jiaxing University  Jiaxing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Oncology Department of Oncology GuangDong Engineering Technology Research Center of Biological Targeting Diagnosis, Therapy and Rehabilitation The Fifth Affiliated Hospital Guangzhou Medical University  Guangzhou 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