A NIR-II Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy

Yishen Liu, Qianqian Li, Meijia Gu, Disheng Lu, Xiaoxing Xiong, Zhiyun Zhang, Yanna Pan, Yuqin Liao, Qihang Ding, Wanxia Gong, Dean Shuailin Chen, Mengting Guan, Junzhu Wu, Zhiquan Tian, Hai Deng, Lijuan Gu*, Xuechuan Hong*, and Yuling Xiao*

Journal of Medicinal Chemistry 2022, 65, 3, 2225–2237

https://doi.org/10.1021/acs.jmedchem.1c01736

Abstract

The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.