Xu Gaofei, Shi Changying, Guo Dandan, Wang Lili, Ling Yun, Han Xiaobing, Luo Juntao
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States; Department of Applied Chemistry, Science College, China Agricultural University, Beijing 100193, China.
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, United States.
Acta Biomater. 2015 Jul;21:85-98. doi: 10.1016/j.actbio.2015.04.021. Epub 2015 Apr 22.
Four coumarin-containing telodendrimers (denoted as P-I, P-II, P-III and P-IV) were designed and synthesized to self-assemble into the corresponding nanoparticles. Of those, two nanoparticles (P-II and P-IV micelles) were screened and selected for targeted drug delivery of 7-ethyl-10-hydroxy camptothecin (SN-38), a prominent and efficacious anticancer agent, for the treatment of colon cancers. The nanoparticle encapsulation significantly increased the solubility of SN-38 in aqueous solution. Dynamic light scattering (DLS) showed the size of these SN-38 nanoparticles to be around 50 nm, and rod-shaped micelles were observed using transmission electron microscopy (TEM). These two novel nanoformulations of SN-38/P-II and SN-38/P-IV were found to exhibit similar in vitro cytotoxic activity against colon cancer cells as the free drug (SN-38 in DMSO) and were 500-fold more potent than irinotecan (a prodrug of SN-38). In addition, near infrared fluorescent (NIRF) optical imaging was utilized to monitor the tumor targeted delivery of SN-38/NPs via co-loading a NIRF dye. It was demonstrated that these NPs preferentially accumulated in tumors when compared to healthy tissue. A pharmacokinetics study showed that SN-38 micelle formulations had a longer circulating time in blood than irinotecan. Furthermore, SN-38 loaded nanoformulations exhibit superior anti-tumor efficacy when compared with irinotecan at equivalent SN-38 dose in HT-29 human colon cancer xenograft models.
设计并合成了四种含香豆素的端基树枝状聚合物（分别记为P-I、P-II、P-III和P-IV），使其自组装成相应的纳米颗粒。其中，筛选并选择了两种纳米颗粒（P-II和P-IV胶束）用于7-乙基-10-羟基喜树碱（SN-38，一种显著且有效的抗癌药物）的靶向给药，以治疗结肠癌。纳米颗粒包封显著提高了SN-38在水溶液中的溶解度。动态光散射（DLS）显示这些SN-38纳米颗粒的尺寸约为50nm，并且使用透射电子显微镜（TEM）观察到棒状胶束。发现这两种新型的SN-38/P-II和SN-38/P-IV纳米制剂对结肠癌细胞表现出与游离药物（DMSO中的SN-38）相似的体外细胞毒性活性，并且比伊立替康（SN-38的前体药物）强500倍。此外，通过共负载近红外荧光（NIRF）染料，利用近红外荧光光学成像来监测SN-38/纳米颗粒的肿瘤靶向递送。结果表明，与健康组织相比，这些纳米颗粒优先在肿瘤中积累。药代动力学研究表明，SN-38胶束制剂在血液中的循环时间比伊立替康长。此外，在HT-29人结肠癌异种移植模型中，与等效SN-38剂量的伊立替康相比，负载SN-38的纳米制剂表现出优异的抗肿瘤疗效。
