无载体混合纳米颗粒通过逆转缺氧和氧化抗性增强口腔癌的光动力疗法

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Suppr 超能文献

核心技术专利：CN118964589B侵权必究

Li Xiao, Li Zhiyin, Su Yue, Zhou Jia, Li Yuxiang, Zhao Qianqian, Yang Xia, Shi Leilei, Shen Lingyue

Department of Cleft Palate Speech, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

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.

Pharmaceutics. 2024 Aug 27;16(9):1130. doi: 10.3390/pharmaceutics16091130.

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 '-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe 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 (O) would be enhanced by the synergy effect on the Fenton reaction of Fe 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.

在本研究中，我们开创了一种协同自组装方法，旨在制备无载体混合纳米颗粒，以应对光动力疗法（PDT）中厌氧微环境和还原型谷胱甘肽（GSH）诱导的抗氧化性所带来的固有挑战。在这些纳米颗粒中，原卟啉IX（PP）、缺氧诱导因子-1α抑制剂“-(2,5-二氯磺酰基)胱胺KC7F2（KC）和辅因子铁之间存在氢键和配位相互作用。这些纳米颗粒表现出被CAL-27细胞高效摄取的特性，通过增强的渗透和滞留（EPR）效应促进其在肿瘤中的积累。在650 nm光照下，铁离子对芬顿反应的协同作用以及缺氧诱导因子-1α的下调会增强细胞毒性单线态氧（O）的形成，从而在体外和体内生物学研究中提高光动力疗法的疗效。我们的工作开辟了一种新的超分子方法来制备混合纳米颗粒，用于与光动力疗法协同有效地治疗癌细胞。