一种基于碳纳米管的铂-吖啶杂化抗癌药物递送系统的设计及细胞研究
Design and cellular studies of a carbon nanotube-based delivery system for a hybrid platinum-acridine anticancer agent.
作者信息
Fahrenholtz Cale D, Ding Song, Bernish Brian W, Wright Mariah L, Zheng Ye, Yang Mu, Yao Xiyuan, Donati George L, Gross Michael D, Bierbach Ulrich, Singh Ravi
机构信息
Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Department of Chemistry, Wake Forest University, Winston-Salem, NC 27109, USA.
出版信息
J Inorg Biochem. 2016 Dec;165:170-180. doi: 10.1016/j.jinorgbio.2016.07.016. Epub 2016 Jul 27.
A three-component drug-delivery system has been developed consisting of multi-walled carbon nanotubes (MWCNTs) coated with a non-classical platinum chemotherapeutic agent ([PtCl(NH)(L)]Cl (P3A1; L=N-(2-(acridin-9-ylamino)ethyl)-N-methylproprionimidamide) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-5000] (DSPE-mPEG). The optimized P3A1-MWCNTs are colloidally stable in physiological solution and deliver more P3A1 into breast cancer cells than treatment with the free drug. Furthermore, P3A1-MWCNTs are cytotoxic to several cell models of breast cancer and induce S-phase cell cycle arrest and non-apoptotic cell death in breast cancer cells. By contrast, free P3A1 induces apoptosis and allows progression to G2/M phase. Photothermal activation of P3A1-MWCNTs to generate mild hyperthermia potentiates their cytotoxicity. These findings suggest that delivery of P3A1 to cancer cells using MWCNTs as a drug carrier may be beneficial for combination cancer chemotherapy and photothermal therapy.
一种由多壁碳纳米管（MWCNTs）组成的三组分药物递送系统已被开发出来，该多壁碳纳米管涂覆有一种非经典铂类化疗药物（[PtCl(NH)(L)]Cl（P3A1；L = N-(2-(吖啶-9-基氨基)乙基)-N-甲基丙酰亚胺酰胺）和1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺-N-[氨基（聚乙二醇）-5000]（DSPE-mPEG）。优化后的P3A1-MWCNTs在生理溶液中具有胶体稳定性，并且比游离药物治疗能将更多的P3A1递送至乳腺癌细胞。此外，P3A1-MWCNTs对几种乳腺癌细胞模型具有细胞毒性，并在乳腺癌细胞中诱导S期细胞周期停滞和非凋亡性细胞死亡。相比之下，游离的P3A1诱导细胞凋亡并使细胞进展至G2/M期。P3A1-MWCNTs的光热激活以产生轻度热疗可增强其细胞毒性。这些发现表明，使用MWCNTs作为药物载体将P3A1递送至癌细胞可能有利于联合癌症化疗和光热疗法。
Zotero 插件