Metronidazole-modified Au@BSA nanocomposites for dual sensitization of radiotherapy in solid tumors.

Autor: Du Q; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China., Yuen HY; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong 999077, China. xin.zhao@polyu.edu.hk., Pan J; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China., Sun C; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China., Wu D; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China., Liu J; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China., Wu G; Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, China. wuguohua@zju.edu.cn., Zhao X; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong 999077, China. xin.zhao@polyu.edu.hk., Wang S; College of Biomedical Engineering, Sichuan University, Chengdu 610065, China. shuqi@scu.edu.cn.; National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.; Tianfu Jincheng Laboratory, City of Future Medicine, Chengdu 641400, China.; Clinical Research Center for Respiratory Disease, West China Hospital, Sichuan University, Chengdu 610065, China.
Jazyk: angličtina
Zdroj: Journal of materials chemistry. B [J Mater Chem B] 2024 Oct 02; Vol. 12 (38), pp. 9686-9694. Date of Electronic Publication: 2024 Oct 02.
DOI: 10.1039/d4tb00910j
Abstrakt: The hypoxic microenvironment of solid tumors can lead to reduced therapeutic DNA damage to the tumor cells, thus diminishing tumor sensitivity to radiotherapy. Although hypoxic radiosensitizers can improve radiotherapy efficacy by enhancing the role of oxygen, their effects are limited by the uneven distribution of oxygen within solid tumor tissues. In this study, a novel radiosensitizer via leveraging gold complexes and metronidazole (MN) was synthesized to improve radiotherapeutic efficacy. The gold atoms incorporated in the radiosensitizer enabled efficient deposition of high-energy radiation; the hydrophobic metronidazole was reduced to hydrophilic aminoimidazole under hypoxia conditions and further promoted radiotherapy sensitization. The results of CCK-8 assays, Live/Dead assays, γ-H 2 AX immunofluorescence indicated that metronidazole-modified Au@BSA nanocomposites (NCs) exhibited excellent antitumor effects. The in vivo antitumor tests further showed an inhibition rate of 100%. These results demonstrated that the NCs successfully enhanced radiotherapy efficacy by the dual sensitization strategy. Overall, we believe this multimodal radiosensitizing nanocomplex can significantly inhibit tumor growth and metastasis, with their hypoxia-oriented characteristics ensuring a higher efficacy and safety.
Databáze: MEDLINE