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

卡巴齐塔塞尔 化学 癌症研究 体内 细胞培养 细胞毒性 细胞凋亡 有丝分裂 癌细胞 体外 癌症 生物 前列腺癌 细胞生物学 生物化学 雄激素剥夺疗法 遗传学 生物技术
作者
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
出处
期刊:Biomedicine & Pharmacotherapy [Elsevier]
卷期号:116: 109001-109001 被引量:14
标识
DOI:10.1016/j.biopha.2019.109001
摘要

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.
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