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pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1\u03b1 inhibitor of N, N\u02b9-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+ present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ ion and the downregulation of the HIF-1\u03b1, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.<\/jats:p>","DOI":"10.3390\/pharmaceutics16091130","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"1130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Carrier-Free Hybrid Nanoparticles for Enhanced Photodynamic Therapy in Oral Carcinoma via Reversal of Hypoxia and Oxidative Resistance"],"prefix":"10.3390","volume":"16","author":[{"given":"Xiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cleft Palate Speech, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Su","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Radiology, Shanghai Sixth People\u2019s Hospital Affiliated to Shang Hai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology, Shanghai Sixth People\u2019s Hospital Affiliated to Shang Hai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Shi","sequence":"additional","affiliation":[{"name":"Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyue","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People\u2019s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Center of Head and Neck Oncology Clinical and Translational Science, Shanghai 200011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104551","DOI":"10.1016\/j.oraloncology.2019.104551","article-title":"Global patterns and trends in cancers of the lip, tongue and mouth","volume":"102","author":"Bray","year":"2020","journal-title":"Oral Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.biopha.2018.07.114","article-title":"Preventive measures in oral cancer: An overview","volume":"107","author":"Addepalli","year":"2018","journal-title":"Biomed. 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