Carrier-Free Hybrid Nanoparticles for Enhanced Photodynamic Therapy in Oral Carcinoma via Reversal of Hypoxia and Oxidative Resistance
Xiao Li,
Zhiyin Li,
Yue Su,
Jia Zhou,
Yuxiang Li,
Qianqian Zhao,
Xia Yang,
Leilei Shi,
Lingyue Shen
Affiliations
Xiao Li
Department of Cleft Palate Speech, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
Zhiyin Li
Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People’s 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
Yue Su
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
Jia Zhou
Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shang Hai Jiao Tong University School of Medicine, Shanghai 200025, China
Yuxiang Li
School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
Qianqian Zhao
Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shang Hai Jiao Tong University School of Medicine, Shanghai 200025, China
Xia Yang
Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People’s 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
Leilei Shi
Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
Lingyue Shen
Department of Oral and Maxillofacial-Head and Neck Oncology, Department of Laser and Aesthetic Medicine, Shanghai Ninth People’s 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
In the present work, we 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-1α inhibitor of N, Nʹ-(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-1α, 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.
