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

  • Biomed Pharmacother. 2019 Aug;116:109001. doi: 10.1016/j.biopha.2019.109001.
Yu Zheng  1 Ting Lan  2 Di Wei  1 Geng Zhang  1 Guangdong Hou  1 Jiarui Yuan  3 Fei Yan  1 Fuli Wang  1 Ping Meng  1 Xiaojian Yang  1 Guo Chen  4 Zheng Zhu  1 Zifan Lu  4 Wei He  5 Jianlin Yuan  6
Affiliations
  • 1. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
  • 2. Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
  • 3. St. George's University School of Medicine, West Indies, Grenada.
  • 4. State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China.
  • 5. Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. Electronic address: [email protected].
  • 6. Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shaanxi Province, China. Electronic address: [email protected].
Abstract

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.

Keywords
Chemotherapy; Near-infrared fluorescent dye; Organic anion-transporting polypeptide; Renal cell carcinoma.
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