Shin Jung Min, Choi Gwan Hyun, Song Seok Ho, Ko Hyewon, Lee Eun Sook, Lee Jae Ah, Yoo Pil J, Park Jae Hyung
School of Chemical Engineering, College of Engineering, Sungkyunkwan University, Suwon 16419, Korea.
Department of Health Science and Technology, SAIHST, Sungkyunkwan University, Suwon 16419, Korea.
Pharmaceutics. 2019 Nov 28;11(12):636. doi: 10.3390/pharmaceutics11120636.
Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy.
尽管自组装纳米颗粒（SNPs）已被广泛用于靶向药物递送，但由于大多数药物在到达靶位点之前就释放到血液中，其临床应用受到了限制。在本研究中，制备了由两亲性透明质酸衍生物组成的金属-酚网络（MPN）包覆的SNPs（MPN-SNPs），作为一种pH响应性纳米载体，以促进药物在肿瘤微环境（TME）中释放。由于其两亲性，SNPs能够包封作为模型抗癌药物的阿霉素（DOX）。将单宁酸和FeCl添加到DOX-SNPs表面，使其能够容易地被MPNs包覆作为扩散屏障。pH敏感的MPN冠层允许DOX在模拟TME的微酸性条件（pH 6.5）下快速释放，并使细胞有效摄取SNPs，在该条件下透明质酸暴露以促进受体介导的内吞作用。负载DOX的MPN-SNPs对癌细胞表现出更高的细胞毒性，表明它们在靶向癌症治疗中作为药物载体的潜在用途。
