Coupling the near-infrared fluorescent dye IR-780 with cabazitaxel makes renal cell carcinoma chemotherapy possible.

Renal cell carcinoma (RCC) has always been considered resistant to chemotherapy. IR-780 is a near-infrared fluorescent (NIRF) dye that can be efficiently taken up by RCC cells. Cabazitaxel is a cytotoxic drug that interferes with mitosis by acting on tubulin. We chemically fused IR-780 and cabazitaxel into a new drug, Caba-780, which is expected to increase the sensitivity of RCC to chemotherapy. Infrared spectrum, nuclear magnetic resonance spectra, high-resolution mass spectra, and IR spectra were used for detecting structural characterization of the new synthetic drug Caba-780. The RCC cells lines ACHN and 786-O, as well as the non-cancerous human embryonic kidney cell line HEK293, were used to assess the cytotoxicity and tumor-efficient uptake of Caba-780 in vitro. The xenograft tumor-bearing mice and C57 mice were used to estimate the tumor-efficient imaging of Caba-780 as well as the safety and efficacy of its anti-tumor effects in vivo. The new synthetic drug Caba-780 retains the NIRF properties of IR-780. In vitro, Caba-780 was efficiently absorbed by the RCC cell lines ACHN and 786-O, and had an inhibitory effect on their growth, clonogenicity migration, and invasion. At the same time, Caba-780 retained the anti-tumor effect of cabazitaxel, which can inhibit the growth of tumor cells and promote apoptosis by inhibiting mitosis. In vivo experiments showed that Caba-780 can be taken up and imaged in tumor tissue, whereby it inhibits tumor growth. The novel fused molecule Caba-780 has application prospects in the diagnosis and treatment of RCC and makes RCC chemotherapy possible.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2019 May 25 [Epub ahead of print]

Yu Zheng, Ting Lan, Di Wei, Geng Zhang, Guangdong Hou, Jiarui Yuan, Fei Yan, Fuli Wang, Ping Meng, Xiaojian Yang, Guo Chen, Zheng Zhu, Zifan Lu, Wei He, Jianlin Yuan

Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China., Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China., St. George's University School of Medicine, West Indies, Grenada., State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China., Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. Electronic address: ., Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. Electronic address: .