{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T23:11:40Z","timestamp":1776294700250,"version":"3.50.1"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The application of photodynamic therapy (PDT) is limited by unsatisfactory therapeutic efficacy and dose-dependent phototoxicity in clinical settings. Intravenous nano-drug delivery systems (NDDSs) hold promise for enhancing the delivery efficiency of photosensitive drugs, but often result in aggregation-caused quenching (ACQ) effects, preventing site-specific activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We exploited manganese (Mn<jats:sup>2+<\/jats:sup>)\u2013pyrochloric acid (PPa) nanocomplexes coordinated using the photosensitizer PPa and metal Mn ion for the treatment of osteosarcoma. The nanocomplexes were precisely co-assembled in water to stably co-deliver Mn<jats:sup>2+<\/jats:sup> and PPa, enabling tumor-specific release and fluorescence recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following laser irradiation, the activated PPa significantly enhanced the killing effects on primary cancer cells. Additionally, Mn<jats:sup>2+<\/jats:sup> ions activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, promoting maturation of dendritic cells (DCs) and augmenting CD8<jats:sup>+<\/jats:sup>-mediated antitumor immune responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This study advances the on-demand activation of photosensitive drugs and photodynamic immunotherapy toward clinical applicability by exploiting Mn<jats:sup>2+<\/jats:sup>\u2013PPa nanocomplexes with high activatability and effectiveness for targeted PDT and immunotherapy.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbioe.2024.1485549","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T08:52:36Z","timestamp":1739782356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Manganese-pyrochloric acid photosensitizer nanocomplexes against osteosarcoma: achieving both high activatability and high effectiveness"],"prefix":"10.3389","volume":"12","author":[{"given":"Xuran","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"122460","DOI":"10.1016\/j.biomaterials.2023.122460","article-title":"Bioengineered hydrogels enhance ex vivo preservation of patient-derived tumor explants for drug evaluation","volume":"305","author":"Adine","year":"2024","journal-title":"Biomaterials"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e2302575","DOI":"10.1002\/smll.202302575","article-title":"Amplified ferroptosis and Apoptosis facilitated by differentiation therapy efficiently suppress the progression of osteosarcoma","volume":"19","author":"He","year":"2023","journal-title":"Small Weinheim der Bergstrasse, Ger."},{"key":"B3","doi-asserted-by":"publisher","first-page":"5877","DOI":"10.7150\/thno.73714","article-title":"Single-cell transcriptomics reveals the regulative roles of cancer associated fibroblasts in tumor immune microenvironment of recurrent osteosarcoma","volume":"12","author":"Huang","year":"2022","journal-title":"Theranostics"},{"key":"B4","doi-asserted-by":"publisher","first-page":"434","DOI":"10.7150\/thno.67300","article-title":"Recent advances in nanomedicines for photodynamic therapy (PDT)-driven cancer immunotherapy","volume":"12","author":"Ji","year":"2022","journal-title":"Theranostics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"20220141","DOI":"10.1002\/exp.20220141","article-title":"Small-molecule nanoprodrug with high drug loading and EGFR, PI3K\/AKT dual-inhibiting properties for bladder cancer treatment","volume":"3","author":"Li","year":"","journal-title":"Explor. (Beijing, China)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"104142","DOI":"10.1016\/j.ebiom.2022.104142","article-title":"METTL14-mediated epitranscriptome modification of MN1 mRNA promote tumorigenicity and all-trans-retinoic acid resistance in osteosarcoma","volume":"82","author":"Li","year":"2022","journal-title":"EBioMedicine"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e2206779","DOI":"10.1002\/advs.202206779","article-title":"Tantalum-zirconium Co-doped metal-organic frameworks sequentially sensitize radio-radiodynamic-immunotherapy for metastatic osteosarcoma","volume":"10","author":"Li","year":"","journal-title":"Adv. Sci. Weinheim, Baden-Wurttemberg, Ger."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e2205511","DOI":"10.1002\/smll.202205511","article-title":"RhRu alloy-anchored MXene nanozyme for synergistic osteosarcoma therapy","volume":"19","author":"Liang","year":"2023","journal-title":"Small Weinheim der Bergstrasse, Ger."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.jconrel.2023.11.058","article-title":"Nanoplatform-enhanced photodynamic therapy for the induction of immunogenic cell death","volume":"365","author":"Liu","year":"2024","journal-title":"J. Control. release official J. Control. Release Soc."},{"key":"B10","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1186\/s12951-023-01961-9","article-title":"Biodegradable FePS(3) nanoplatform for efficient treatment of osteosarcoma by combination of gene and NIR-II photothermal therapy","volume":"21","author":"Luo","year":"2023","journal-title":"J. nanobiotechnology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"20230050","DOI":"10.1002\/exp.20230050","article-title":"Designing advanced S-scheme CdS QDs\/La-Bi(2)WO(6) photocatalysts for efficient degradation of RhB","volume":"3","author":"Ning","year":"2023","journal-title":"Explor. (Beijing, China)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2974","DOI":"10.3390\/ijms25052974","article-title":"Photodynamic therapy and cardiovascular diseases","volume":"25","author":"Oskroba","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e284","DOI":"10.1016\/s1470-2045(23)00155-9","article-title":"Extraskeletal osteosarcoma of primary retroperitoneal origin","volume":"24","author":"Sapiano","year":"2023","journal-title":"Lancet. Oncol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e2303911","DOI":"10.1002\/adhm.202303911","article-title":"MOF@COF nanocapsules enhance soft tissue sarcoma treatment: synergistic effects of photodynamic therapy and PARP inhibition on tumor growth suppression and immune response activation","volume":"13","author":"Tai","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"B15","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41413-023-00246-z","article-title":"Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment","volume":"11","author":"Tian","year":"2023","journal-title":"Bone Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e2308539","DOI":"10.1002\/smll.202308539","article-title":"Manipulating redox homeostasis of cancer stem cells overcome chemotherapeutic resistance through photoactivatable biomimetic nanodiscs","volume":"20","author":"Wang","year":"","journal-title":"Small Weinheim der Bergstrasse, Ger."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e2307143","DOI":"10.1002\/advs.202307143","article-title":"A NRF2 regulated and the immunosuppressive microenvironment reversed nanoplatform for cholangiocarcinoma photodynamic-gas therapy","volume":"11","author":"Wang","year":"","journal-title":"Adv. Sci. Weinheim, Baden-Wurttemberg, Ger."},{"key":"B18","doi-asserted-by":"publisher","first-page":"6252","DOI":"10.1021\/jacs.3c14387","article-title":"Enhancing fractionated cancer therapy: a triple-anthracene photosensitizer unleashes long-persistent photodynamic and luminous efficacy","volume":"146","author":"Wang","year":"","journal-title":"J. Am. Chem. Soc."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6247","DOI":"10.1021\/acsnano.2c09685","article-title":"Chemotherapy-sensitized in situ vaccination for malignant osteosarcoma enabled by bioinspired calcium phosphonate nanoagents","volume":"17","author":"Wang","year":"2023","journal-title":"ACS nano"},{"key":"B20","doi-asserted-by":"publisher","first-page":"5272","DOI":"10.7150\/thno.73566","article-title":"Progress in advanced nanotherapeutics for enhanced photodynamic immunotherapy of tumor","volume":"12","author":"Wei","year":"2022","journal-title":"Theranostics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5086","DOI":"10.7150\/thno.74989","article-title":"UBR5 promotes tumor immune evasion through enhancing IFN-\u03b3-induced PDL1 transcription in triple negative breast cancer","volume":"12","author":"Wu","year":"2022","journal-title":"Theranostics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"16192","DOI":"10.1021\/acsnano.3c05463","article-title":"Manipulating neovasculature-targeting capability of biomimetic nanodiscs for synergistic photoactivatable tumor infarction and chemotherapy","volume":"17","author":"Xu","year":"2023","journal-title":"ACS nano"},{"key":"B23","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s12943-022-01624-7","article-title":"Circular RNA circFIRRE drives osteosarcoma progression and metastasis through tumorigenic-angiogenic coupling","volume":"21","author":"Yu","year":"2022","journal-title":"Mol. cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4691","DOI":"10.1182\/bloodadvances.2021006169","article-title":"Nurselike cells sequester B cells in disorganized lymph nodes in chronic lymphocytic leukemia via alternative production of CCL21","volume":"6","author":"Zaaboub","year":"2022","journal-title":"Blood Adv."},{"key":"B25","doi-asserted-by":"publisher","first-page":"121433","DOI":"10.1016\/j.biomaterials.2022.121433","article-title":"Emerging photodynamic nanotherapeutics for inducing immunogenic cell death and potentiating cancer immunotherapy","volume":"282","author":"Zhang","year":"2022","journal-title":"Biomaterials"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e008054","DOI":"10.1136\/jitc-2023-008054","article-title":"Mitochondria-targeted photodynamic therapy triggers GSDME-mediated pyroptosis and sensitizes anti-PD-1 therapy in colorectal cancer","volume":"12","author":"Zhou","year":"2024","journal-title":"J. Immunother. cancer"}],"container-title":["Frontiers in Bioengineering and Biotechnology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1485549\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T08:52:38Z","timestamp":1739782358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fbioe.2024.1485549\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":26,"alternative-id":["10.3389\/fbioe.2024.1485549"],"URL":"https:\/\/doi.org\/10.3389\/fbioe.2024.1485549","relation":{},"ISSN":["2296-4185"],"issn-type":[{"value":"2296-4185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]},"article-number":"1485549"}}