A Second Near-Infrared Ru(II) Polypyridyl Complex for Synergistic Chemo-Photothermal Therapy.

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

Journal: Journal of medicinal chemistry 2022;65(3):2225-2237

PMID: 34994554

Full Text on American Chemical Society View on PubMed

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-]quinoxaline into a novel second near-infrared (NIR-II) fluorophore . After PEGylation and chelation, 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. displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.

Address: Department of Neurosurgery, Central Laboratory, Renmin Hospital of Wuhan University, State Key Laboratory of Virology, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.; College of Science, Laboratory of Extreme Environmental Biological Resources and Adaptive Evolution, Research Center for Ecology, Tibet University, Lhasa 850000, China.; Shenzhen Institute of Wuhan University, Shenzhen 518057, China.; Center for Experimental Basic Medical Education, Hubei Provincial Key Laboratory of Developmentally Originated Disease and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE), Wuhan 430071, China.; Hubei Key Laboratory for Processing and Application of Catalytic Materials, Huanggang Normal University, Huanggang 438000, China.; Department of Chemistry, Pennsylvania State University, Philadelphia, Pennsylvania 19104, United States.; Department of Chemistry, University of Aberdeen, Aberdeen AB24 3FX, U.K.

DOI: 10.1021/acs.jmedchem.1c01736

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

MeSH Terms: Apoptosis, Biocompatible Materials, Cell Line, Tumor, Coordination Complexes, Drug Design, Fluorescent Dyes, G2 Phase Cell Cycle Checkpoints, Humans, Hyperthermia, Induced, Infrared Rays, Neoplasms, Phenazines, Photothermal Therapy, Polyethylene Glycols, Quantum Theory, Ruthenium, Spectroscopy, Near-Infrared