Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology, and Department of Radiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.
Biomater Sci. 2020 Jun 21;8(12):3485-3499. doi: 10.1039/d0bm00295j. Epub 2020 May 20.
Sorafenib (SF) is the first drug demonstrated to improve the survival of patients diagnosed with advanced-stage hepatocellular carcinoma (HCC). However, its clinical application is limited by the poor oral bioavailability and severe side effects. In this study, a multifunctional micellar nanodrug was developed for simultaneous HCC-targeted delivery of SF and tumor detection with magnetic resonance imaging (MRI). The micellar nanodrug incorporating SF and superparamagnetic iron oxide nanoparticles (SPIONs) was prepared from a diblock copolymer of monomethoxyl poly(ethylene glycol) and poly(N-(2-aminoethanethiol-co-2-aminoethyldiisopropylamine) aspartamide) and then decorated with anti-glypican-3 antibody (Ab). Owing to the small size, weak positive charge and Ab-mediated active targeting to HCC cells, the nanodrug exhibited an easy cellular uptake and enhanced tumor accumulation. The prominent reduction and pH dual-sensitivity allowed the nanodrug to rapidly release SF inside cancer cells via responding to the cytoplasmic glutathione and lysosomal acidity. The nanodrug not only significantly improved the anticancer effects of SF in hepatoma treatment but also facilitated a noninvasive tumor detection and monitoring of in vivo drug delivery by MRI, which revealed its great potential as a promising theranostic system.
索拉非尼（SF）是首个被证明可改善晚期肝细胞癌（HCC）患者生存的药物。然而，其临床应用受到口服生物利用度差和严重副作用的限制。在本研究中，开发了一种多功能胶束纳米药物，用于同时将 SF 和磁共振成像（MRI）进行肿瘤检测递送到 HCC。该胶束纳米药物由单甲氧基聚乙二醇和聚（N-（2-氨基乙硫醇-2-乙胺基二异丙基）天冬酰胺）的嵌段共聚物制备而成，并将其与抗磷脂酰基丝氨酸抗体（Ab）进行了修饰。由于其尺寸小、带微弱正电荷以及 Ab 介导的 HCC 细胞的主动靶向作用，该纳米药物表现出易于细胞摄取和增强的肿瘤积累。显著的还原和 pH 双重敏感性使得纳米药物能够通过响应细胞质谷胱甘肽和溶酶体酸度，在癌细胞内迅速释放 SF。该纳米药物不仅显著提高了 SF 在肝癌治疗中的抗癌效果，而且还通过 MRI 实现了对肿瘤的非侵入性检测和药物递送的监测，这表明其作为一种有前途的治疗系统具有巨大的潜力。
