Polymeric Micelles Encapsulating Fisetin Improve the Therapeutic Effect in Colon Cancer
Polymeric Micelles Encapsulating Fisetin Improve the Therapeutic Effect in Colon Cancer
复制标题
封装非瑟酮的聚合物胶束提高结肠癌的治疗效果
DOI：
10.1021/am5066893
复制
发表时间：
2015-01-14
影响因子：
9.5
通讯作者：
Gong, Changyang
中科院分区：
文献类型：
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作者：
Chen, Yishan;Wu, Qinjie;Gong, Changyang
天然黄酮类化合物非瑟酮（3，3 ′，4 ′，7-tetrahydroxyflavone）被发现具有抗肿瘤活性，显示了其在未来化疗中的潜在价值。然而，其较差的水溶性使得其难以静脉内施用。本研究以单甲基聚乙二醇-聚己内酯（MPEG-PCL）共聚物为载体，通过自组装方法制备了非瑟酮纳米组装体。制备的非瑟酮胶束平均粒径为22 ± 3 nm，多分散指数为0.163 ± 0.032，载药量为9.88 ± 0.14%，包封率为98.53 ± 0.02%。与游离非瑟酮相比，非瑟酮胶束具有较长的体外释药时间和较强的细胞毒活性，并能增强非瑟酮对CT 26细胞的摄取和诱导细胞凋亡。在体内研究中，非瑟酮胶束在皮下CT 26肿瘤模型中比游离非瑟酮更能抑制肿瘤生长和延长存活时间。组织学分析、末端脱氧核苷酸转移酶介导的缺口末端标记法、Ki-67免疫组化检测和微血管密度检测表明，非瑟酮胶束具有增强的肿瘤细胞凋亡诱导、增殖抑制和抗血管生成活性。综上所述，我们成功地制备了一种基于MPEG-PCL的纳米载体，该纳米载体包封非瑟酮，具有增强的抗肿瘤活性。
The natural flavonoid fisetin (3,3′,4′,7-tetrahydroxyflavone) was discovered to possess antitumor activity, revealing its potential value in future chemotherapy. However, its poor water solubility makes it difficult for intravenous administration. In this study, the monomethyl poly(ethylene glycol)–poly(ε-caprolactone) (MPEG–PCL) copolymer was applied to prepare nanoassemblies of fisetin by a self-assembly procedure. The prepared fisetin micelles gained a mean particle size of 22 ± 3 nm, polydisperse index of 0.163 ± 0.032, drug loading of 9.88 ± 0.14%, and encapsulation efficiency of 98.53 ± 0.02%. Compared with free fisetin, fisetin micelles demonstrated a sustained and prolongedin vitrorelease behavior, as well as enhanced cytotoxicity, cellular uptake, and fisetin-induced apoptosis in CT26 cells. As forin vivostudies, fisetin micelles were more competent for suppressing tumor growth and prolonging survival time than free fisetin in the subcutaneous CT26 tumor model. Furthermore, histological analysis, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay, immunohistochemical detection ofKi-67, and microvessel density detection were conducted, demonstrating that fisetin micelles gained increased tumor apoptosis induction, proliferation suppression, and antiangiogenesis activities. In conclusion, we have successfully produced a MPEG–PCL-based nanocarrier encapsulating fisetin with enhanced antitumor activity.