Multi‐responsive mesoporous polydopamine composite nanorods cooperate with nano‐enzyme and photosensitiser for intensive immunotherapy of bladder cancer

• Published in: Immunology Vol. 167; no. 2; pp. 247 - 262
• Main Authors: Wu, Xiang, Wei, Yongbao, Lin, Rongcheng, Chen, Pingzhou, Hong, Zhiwei, Zeng, Rong, Xu, Qingjiang, Li, Tao
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.10.2022
• Subjects: adhesion property; Adhesive strength; Biocompatibility; Bladder; Bladder cancer; Cancer; Charge reversal; composite nanorods; Cooperation; Drug delivery; Enzymes; Hydrogen peroxide; Hypoxia; Immunotherapy; Infrared radiation; Malignancy; Manganese; Manganese dioxide; Microenvironments; Nanoparticles; Nanorods; nano‐enzyme; Oxygen; PD-L1 protein; photothermal agent; Singlet oxygen; Toxicity; Tumor microenvironment; Tumors; Urination; Wheat germ; Wheat germ agglutinin
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.13534

Bladder cancer is a common malignancy in the urinary system. Defects of drug molecules in bladder during treatment, such as passive diffusion, rapid clearance of periodic urination, poor adhesion and permeation abilities, lead to low delivery efficiency of conventional drugs and high recurrence rate of disease. In this study, we designed multi‐responsive mesoporous polydopamine (PDA) composite nanorods cooperating with nano‐enzyme and photosensitiser for intensive immunotherapy of bladder cancer. The strongly adhesive mesoporous PDA with wheat germ agglutinin on nanoparticles could specifically adhere to epithelial glycocalyx and made the nanoparticles aggregate in urinary pathways. Meanwhile, 2,3‐dimethylmaleic anhydride could be hydrolysed in acidic conditions of tumour microenvironment, giving it a positive charge (charge reversal), which is more amenable to enter cancer cells. Afterwards, manganese dioxide nanorods could catalyse the reaction of excess H2O2 in tumour microenvironment to generate active oxygen, so as to change the hypoxic environment in tumour, and achieve a pH‐responsive for slow release of PD‐L1. After the ICG was irradiated by infrared light, a large amount of singlet oxygen was generated, thereby enhancing the therapeutic effect and reducing toxicity in vivo. Besides, mesoporous PDA with indocyanine green photothermal agent could have a local heat up quickly under the near‐infrared light to kill cancer cells, thereby enhancing therapeutic efficacy. Accordingly, this mesoporous PDA composite nanorods shed a light on bladder tumour treatment. In this study, we found a mesoporous PDA composite nanorods with dual responses of photothermal and immune for the treatment of bladder cancer. The nanorods work with wheat germ agglutinin to specifically adhere to the superior calyx in the urinary system. Through photothermal pH response and other ways, the nanorods exert killing effect on cancer cells.