MUC1 aptamer-targeted DNA micelles for dual tumor therapy using doxorubicin and KLA peptide
MUC1 aptamer-targeted DNA micelles for dual tumor therapy using doxorubicin and KLA peptide
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DOI：
10.1016/j.nano.2017.12.010
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发表时间：
2018-04-01
影响因子：
5.4
通讯作者：
Ramezani, Mohammad
中科院分区：
文献类型：
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作者：
Charbgoo, Fahimeh;Alibolandi, Mona;Ramezani, Mohammad
DNA 纳米粒子的靶向递送是癌症治疗中一种有前景的方法。使用适配体，可以实现 DNA 纳米粒子的目标特异性递送。此外，适体可以间接提高DNA纳米颗粒对插入核酸碱基对的药物的封装效率。使用 DNA 块，制备了胶束混合纳米颗粒，用于将阿霉素和促凋亡肽 KLA 靶向共同递送至肿瘤细胞。结果表明，抗 MUC1 适体可以通过改善细胞摄取，将合成的 DNA 胶束特异性递送至 MCF-7 细胞中。此外，阿霉素和 KLA 的共同递送可以显着增强该构建体的治疗功效，从而减少所需的阿霉素剂量，这是减少化疗副作用的关键点。此外，与游离药物相比，DOX-KLA-抗MUC1-胶束显着抑制荷瘤小鼠的肿瘤生长。 DOX-KLA-抗-MUC1-胶束还降低了游离阿霉素的毒性作用，根据体重减轻百分比和体内存活率确定。 (c) 2018 Elsevier Inc. 保留所有权利。
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. (c) 2018 Elsevier Inc. All rights reserved.