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Herein, we develop a lysosome-bursting calcium carbonate nanoplatform (cRGD\/MD@ICN) co-loaded with the photosensitizer indocyanine green (ICG) and a PD-L1 inhibitory peptide (\n                    <jats:sup>D<\/jats:sup>\n                    PPA-1) for synergistic phototherapy and calcium overload to amplify ICD and potentiate immune checkpoint blockade. The nanoparticle is decorated with cRGD for active tumor targeting and a matrix metalloproteinase-2 (MMP-2)-cleavable linker (MD) for on-demand release of\n                    <jats:sup>D<\/jats:sup>\n                    PPA-1 in the tumor microenvironment. Upon endocytosis into tumor cells, the acidic lysosomal environment triggers rapid dissolution of the calcium carbonate core, releasing ICG and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    , leading to lysosome bursting and subsequent calcium overload. Combined with near-infrared (NIR) irradiation, ICG-mediated phototherapy and calcium overload synergistically induce robust ICD, characterized by enhanced calreticulin exposure, HMGB1 release, and ATP secretion. In\u00a0vivo studies demonstrate that cRGD\/MD@ICN significantly suppresses orthotopic breast tumor growth and pulmonary metastasis by promoting dendritic cell maturation and intratumoral infiltration of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. This lysosome-bursting nanoplatform offers a promising strategy to amplify ICD through synergistic phototherapy and calcium overload, thereby boosting the efficacy of immune checkpoint blockade for cancer treatment.\n                  <\/jats:p>","DOI":"10.34133\/research.1444","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T16:37:08Z","timestamp":1789058228000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":0,"title":["Lysosome-Bursting Calcium Carbonate Nanoparticles Amplify Immunogenic Cell Death via Synergistic Phototherapy and Calcium Overload for Immune Checkpoint Blockade"],"prefix":"10.34133","volume":"9","author":[{"given":"Feifei","family":"Cui","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifan","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."},{"name":"Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfan","family":"Han","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaokun","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dailin","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingrui","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."},{"name":"Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and KLMDASR of Tianjin, \rNankai University, Tianjin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-6154","authenticated-orcid":true,"given":"Jun","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."},{"name":"Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, \rChinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2026,10,12]]},"reference":[{"issue":"6","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/nri.2017.48","article-title":"Immunosuppressive cell death in cancer","volume":"17","author":"Galluzzi L","year":"2017","unstructured":"Galluzzi L, Hou J, Greten TF, Xia Q. 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