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MUC1 适体靶向 DNA 胶束用于多柔比星和 KLA 肽的双重肿瘤治疗。

MUC1 aptamer-targeted DNA micelles for dual tumor therapy using doxorubicin and KLA peptide.

机构信息

Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Nanomedicine. 2018 Apr;14(3):685-697. doi: 10.1016/j.nano.2017.12.010. Epub 2018 Jan 6.

Abstract

Targeted delivery of DNA nanoparticles is a promising approach in cancer therapy. Using aptamers, target specific delivery of DNA nanoparticles can be achieved. Further, aptamers can indirectly improve drug encapsulation efficiency of DNA nanoparticles for drugs intercalated within nucleic acid base pairs. Using DNA blocks, a micellar hybrid nanoparticle was prepared for the targeted co-delivery of doxorubicin and a pro-apoptotic peptide, KLA to tumor cells. Results demonstrated that anti-MUC1 aptamer could specifically deliver the synthesized DNA micelle into MCF-7 cells by improving its cellular uptake. Additionally, co-delivery of doxorubicin and KLA could significantly enhance the therapeutic efficacy of the construct resulting in reduction of required dose of doxorubicin that is a pivotal point in reducing chemotherapeutics side effects. Moreover, DOX-KLA-anti-MUC1-micelle remarkably inhibited tumor growth of tumor-bearing mice when compared with free drug. DOX-KLA-anti-MUC1-micelle also reduced toxic effect of free doxorubicin as determined by percent of body weight loss and survival rate in vivo.

摘要

靶向递送 DNA 纳米颗粒是癌症治疗中很有前途的方法。使用适体可以实现 DNA 纳米颗粒的靶向特异性递送。此外,适体还可以间接提高 DNA 纳米颗粒对药物的包封效率,因为药物可以插入核酸碱基对之间。使用 DNA 块,制备了一种胶束杂化纳米颗粒,用于将阿霉素和促凋亡肽 KLA 靶向递送至肿瘤细胞。结果表明,抗 MUC1 适体能通过提高细胞摄取率,将合成的 DNA 胶束特异性递送至 MCF-7 细胞。此外,阿霉素和 KLA 的共递送可以显著增强构建体的治疗效果,从而减少所需的阿霉素剂量,这是降低化疗副作用的关键。此外,与游离药物相比,DOX-KLA-anti-MUC1-胶束显著抑制了荷瘤小鼠的肿瘤生长。DOX-KLA-anti-MUC1-胶束还通过体内体重减轻百分比和存活率降低了游离阿霉素的毒性作用。

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