The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging a
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PRECLINICAL STUDIES
The near-infrared fluorescent dye IR-780 was coupled with cabazitaxel for castration-resistant prostate cancer imaging and therapy Yu Zheng 1 & Guangdong Hou 1 & Geng Zhang 1 & Ting Lan 2 & Jiarui Yuan 3 & Lei Zhang 1 & Fei Yan 1 & Fuli Wang 1 & Ping Meng 1 & Xinlong Dun 1 & Xi’an Li 1 & Guo Chen 4 & Zheng Zhu 1 & Di Wei 1 & Wei He 2 & Jianlin Yuan 1 Received: 21 January 2020 / Accepted: 7 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Summary A new drug, Caba-780, was synthesized by chemical coupling of the heptamethyl phthalocyanine near-infrared fluorescent (NIRF) dye IR-780 and the paclitaxel-based chemotherapeutic drug cabazitaxel. Then, the potential value of Caba-780 in the diagnosis and treatment of castration-resistant prostate cancer (CRPC) was evaluated. The CRPC cell lines DU145 and PC-3, as well as the normal human prostate stromal cell line WPMY-1, were used to evaluate the uptake of Caba-780 and its antitumor effect in vitro. The distribution, antitumor effect, and safety of Caba-780 were also evaluated in tumor-bearing mouse xenograft models. Our results showed that Caba-780 was efficiently absorbed by DU145 and PC-3 cells and that the cytotoxicity of Caba780 was significantly stronger than that of IR-780 and cabazitaxel. In addition, Caba-780 inhibited the migration and invasion of DU145 and PC-3 cells and promoted apoptosis by prolonging the G2 phase of the cell cycle. Further analysis indicated that Caba780 could be used to effectively image tumor xenografts. At the same time, this drug inhibited the growth of tumors in vivo. Therefore, the new synthetic drug Caba-780 has potential applications in the diagnosis and treatment of CRPC. Keywords Castration-resistant prostate cancer . Near-infrared fluorescent dye . Chemotherapy . Organic anion-transporting polypeptide
Introduction Yu Zheng, Guangdong Hou, Geng Zhang and Ting Lan contributed equally to this research as co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10637-020-00934-1) contains supplementary material, which is available to authorized users. * Wei He [email protected] * Jianlin Yuan [email protected] 1
Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China
2
Department of Chemistry, School of Pharmacy, Fourth Military Medical University, Xi’an, Shaanxi, China
3
St. George’s University School of Medicine, St. George’s, West Indies, Grenada
4
State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, Fourth Military Medical University, Xi’an, Shaanxi, China
Prostate cancer is the most common malignant tumor in men. Epidemiological investigations predict that there might be approximately 191,930 new cases of prostate cancer and 33,330 deaths due to prostate cancer in the United States in 2020, accounting for 21% and 10% of malignant tumor cases and deaths in men, respectively [1]. In Europe, the incidence and mortality rate of prostate cancer ranks f
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