Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma
Tumor-targeted chemotherapy with the nanopolymer-based drug NC-6004 for oral squamous cell carcinoma
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DOI：
10.1111/cas.12079
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发表时间：
2013-03-01
期刊：
影响因子：
5.7
通讯作者：
Yoshizaki, Tomokazu
中科院分区：
文献类型：
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作者：
Endo, Kazuhira;Ueno, Takayoshi;Yoshizaki, Tomokazu
顺铂（CDDP）已成为头颈部鳞状细胞癌患者化疗的关键药物。肾毒性是其剂量限制的不良反应之一。为了增强其抗肿瘤作用，减少其毒性问题，人们开发了携带CDDP （NC-6004）的聚合物胶束。本研究旨在评价NC-6004治疗口腔鳞状细胞癌的疗效和安全性。测定了四种口腔鳞状细胞癌细胞的体外抗肿瘤活性。为了研究NC-6004的抗肿瘤和肾毒性作用，我们给裸鼠注射NC-6004或CDDP。NC-6004的体外生长抑制作用明显小于CDDP。而NC-6004和CDDP在体内均表现出相当的抗肿瘤作用。CDDP小鼠出现肾细胞凋亡；而注射NC-6004的小鼠几乎没有肾细胞损伤。此外，在使用OSC-19的原位舌癌模型中，NC-6004使前哨淋巴结转移率低于CDDP。综上所述，考虑到NC-6004在显著的抗肿瘤活性、淋巴给药和降低肾毒性方面的潜在优势，NC-6004在铂配合物的开发中具有显著的结构改进。
Cisplatin (CDDP) has been a key drug for chemotherapy in patients with head and neck squamous cell carcinoma. Nephrotoxicity is one of its adverse reactions that are dose limiting. To increase its antitumor effects and reduce such toxicity problems, polymeric micelles carrying CDDP (NC-6004) have been developed. The present study was designed to evaluate the efficacy and safety of NC-6004 for oral squamous cell carcinoma. In vitro antitumor activity was assayed in four oral squamous cell carcinoma cell lines. To investigate the antitumor and nephrotoxic effects of NC-6004, nude mice bearing OSC-19 were administered NC-6004 or CDDP. The in vitro growth-inhibitory effect of NC-6004 was significantly less than that of CDDP. However, both NC-6004 and CDDP showed equivalent antitumor effects in vivo. Mice with CDDP developed renal cell apoptosis; however, those injected with NC-6004 were almost free of renal cell injury. Moreover, in an orthotopic tongue cancer model using OSC-19, NC-6004 reduced the rate of sentinel lymph node metastasis to lower than that with CDDP. In conclusion, considering the potential advantages in terms of noticeable antitumor activity, lymphatic drug delivery and reduced nephrotoxicity, NC-6004 represents a significant structural improvement in the development of a platinum complex.