Ligand Engineering of Titanium-Oxo Nanoclusters for Cerenkov Radiation-Reinforced Photo/Chemodynamic Tumor Therapy

• Published in: ACS applied materials & interfaces Vol. 13; no. 46; pp. 54727 - 54738
• Main Authors: Li, Jingchao, Dai, Shuqi, Qin, Ruixue, Shi, Changrong, Ming, Jiang, Zeng, Xinying, Wen, Xuejun, Zhuang, Rongqiang, Chen, Xiaoyuan, Guo, Zhide, Zhang, Xianzhong
• Format: Journal Article
• Language: English
• Published: United States 24.11.2021
• Subjects: Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Beta Particles; Cell Line; Cell Proliferation - drug effects; Cell Survival - drug effects; Drug Screening Assays, Antitumor; Female; Humans; Ligands; Liver Neoplasms, Experimental - diagnostic imaging; Liver Neoplasms, Experimental - drug therapy; Liver Neoplasms, Experimental - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - chemistry; Optical Imaging; Oxides - chemistry; Oxides - pharmacology; Photochemotherapy; Photosensitizing Agents - chemical synthesis; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology; Titanium - chemistry; Titanium - pharmacology; ligand engineering; nanoclusters; Cerenkov radiation; chemodynamic therapy; photodynamic therapy
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c16213

The therapeutic effect of general photodynamic therapy (PDT) is gravely limited by the poor penetration depth of exogenous light radiation. In recent years, Cerenkov radiation (CR) has been exploringly applied to overcome this critical defect. However, the currently reported type I photosensitizers for CR-induced PDT (CRIT) are only TiO nanoparticle-based agents with numerous fatally intrinsic drawbacks. Herein, we developed NH -Ti O nanocluster (NTOC)-derived ultrasmall nanophotosensitizers (NPSs, denoted as TDPs) via innovate ligand engineering. The introduced dopamine (DA) ligands not only facilitate the water solubility and photocatalytic properties of NPSs but also involve the tumor-targeting behavior through the binding affinity with DA receptors on cancer cells. Under CR irradiation, TDPs enable efficient hydroxyl radical (·OH) generation benefiting from the enhanced separation of hole (h )-electron (e ) pairs, where the h will react with H O to execute type I PDT and the transferred e can realize the augmentation of Ti to substantially promote the therapeutic index of chemodynamic therapy. This study provides an easy but feasible strategy for constructing versatile NPSs with an ultrasmall framework structure, propounding a refreshing paradigm for implementing efficient CR-induced combined therapy (CRICT) and spurring the development of CR and titanium-familial nanoplatforms in the fields of photocatalysis and nanocatalytic medicine.