作者：Jiayu Yu, Jianing Zhang, Jing Jin, Wei Jiang
关键字：DNA, 白蛋白, 纳米载体, 靶向治疗, 微环境响应, 阿霉素
论文来源：期刊
具体来源：Journal of Materials Chemistry B, 2021, 9(40), 8424-8436
发表时间：2021年

摘要：具有精准靶向和高效治疗的药物递送已成为癌症治疗的重要策略。通过点击化学和DNA杂交反应合成了两种基于牛血清白蛋白（BSA）和DNA的纳米载体（DNA-BSA1和DNA-BSA2）。DNA-BSA1中杂交寡核苷酸Linker1包含pH敏感i-motif序列和靶向癌细胞的AS1411适配体序列，DNA-BSA2中Linker2仅含相同pH敏感i-motif序列。阿霉素（DOX）分子可通过非共价相互作用快速优先嵌入双链DNA，DNA-BSA1和DNA-BSA2的包封率分别接近100%和87.5%。作为癌细胞微环境模拟，分别提出了pH触发和脱氧核糖核酸酶I（DNase I）触发释放机制，解释DNA-BSA@DOX在酸性条件和DNase I存在下的动态释放。细胞内摄取和细胞毒性实验证实，由于AS1411对癌细胞过表达核仁素的高亲和力和特异性，DNA-BSA1@DOX对癌细胞具有精准靶向和高效治疗作用。体内研究表明该纳米载体系统可有效抑制肿瘤生长。因此，全生物基纳米载体DNA-BSA是用于抗癌药物负载和释放、精准递送和高效治疗的有前景候选。

Abstract：Drug delivery with accurate targeting and efficient treatment has become an essential strategy for cancer therapy. Two nanocarriers based on bovine serum albumin (BSA) and DNA were synthesized via click chemistry and DNA hybridization reactions (DNA-BSA1 and DNA-BSA2). One of the hybridized oligonucleotides, Linker1, in DNA-BSA1 included a pH-sensitive i-motif sequence and a cancer cell-targeted guanine-quadruplex-structured AS1411 aptamer sequence, and the other, Linker2, in DNA-BSA2 had only the same pH-sensitive i-motif sequence. Doxorubicin (DOX) molecules could be quickly and preferentially intercalated into double-stranded DNA via non-covalent interactions, and the encapsulation efficiency of DNA-BSA1 and DNA-BSA2 was almost 100% and 87.5%, respectively. As a mimic of the cancer cell microenvironment, a pH-trigger and a deoxyribonuclease I (DNase I)-trigger release mechanism was individually proposed to explain the dynamic release of the DNA-BSA@DOX under acidic conditions and the presence of DNase I in vitro. Intracellular uptake and cytotoxicity experiments confirmed that the nanocarrier DNA-BSA1@DOX had accurate targeting and efficient treatment towards cancer cells due to the high affinity and specificity of AS1411 to nucleolin, which is overexpressed in cancer cells. Furthermore, in vivo studies showed that the nanocarrier system could efficiently inhibit tumor growth. Therefore, the entire bio-based nanocarrier DNA-BSA is a promising candidate for the loading and release of anti-cancer drugs for accurate delivery and efficient treatment.

论文链接：https://doi.org/10.1039/d1tb01022k