Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
Colloids Surf B Biointerfaces. 2018 Nov 1;171:24-30. doi: 10.1016/j.colsurfb.2018.07.008. Epub 2018 Jul 5.
Proteins have been extensively explored as versatile nanocarriers for drug delivery due to their complete biocompatibility, ease of surface modification, and lack of toxicity and immunogenicity. In this study, a facile strategy was used to construct aptamer-functionalized albumin-based nanoparticles for effective drug delivery and targeted cancer therapy. A hydrophobic drug, doxorubicin (DOX) was employed to trigger the self-assembly of bovine serum albumin (BSA) to from stable nanoparticles via hydrophobic interaction, and then a tumor targeting aptamer AS1411 was incorporated to the surface of DOX loaded BSA. Due to the specific recognition between AS1411 and its receptor over-expressed on tumor cells, the aptamer-modified nanoparticles show higher cellular uptake and stronger cell inhibitory efficacy against cancerous MCF-7 cells as compared with the nanoparticles without aptamer modification. In addition, DOX loaded aptamer-functionalized nanoparticles can induce more significant down-regulation of Bcl-2 and PCNA as well as up-regulation of pRB, PARP and Bax in MCF-7 cells compared with unmodified nanoparticles, indicating the aptamer modification can induce cell apoptosis more effectively. Besides, aptamer-modified nanoparticles exhibit a significantly improved capability in up-regulating p16, p21 and E-cadherin, and down-regulating EpCAM, vimentin, Snail, MMP-9, CD44 and CD133, implying the favorable effects of drug delivery on the prevention of tumor progression and metastasis.
由于蛋白质具有完全的生物相容性、易于表面修饰、缺乏毒性和免疫原性，因此被广泛探索作为多功能纳米载体用于药物传递。在这项研究中，采用了一种简便的策略来构建适体功能化的基于白蛋白的纳米颗粒，以实现有效的药物传递和靶向癌症治疗。采用疏水性药物阿霉素（DOX）通过疏水相互作用触发牛血清白蛋白（BSA）自组装形成稳定的纳米颗粒，然后将肿瘤靶向适体 AS1411 掺入到 DOX 负载的 BSA 表面。由于 AS1411 与其在肿瘤细胞上过表达的受体之间的特异性识别，与没有适体修饰的纳米颗粒相比，修饰有适体的纳米颗粒显示出更高的细胞摄取率和更强的细胞抑制效力针对癌细胞 MCF-7。此外，与未修饰的纳米颗粒相比，载 DOX 的适体功能化纳米颗粒在 MCF-7 细胞中可诱导更显著地下调 Bcl-2 和 PCNA 以及上调 pRB、PARP 和 Bax，表明适体修饰可以更有效地诱导细胞凋亡。此外，修饰有适体的纳米颗粒在上调 p16、p21 和 E-钙粘蛋白以及下调 EpCAM、波形蛋白、Snail、MMP-9、CD44 和 CD133 方面表现出显著提高的能力，这表明药物传递对预防肿瘤进展和转移具有有利影响。
