Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India.
Colloids Surf B Biointerfaces. 2021 Aug;204:111778. doi: 10.1016/j.colsurfb.2021.111778. Epub 2021 Apr 20.
Hepatocellular carcinoma (HCC) is the most common hepatic malignancy worldwide. Recent reports focusing on the efficacy of apigenin-loaded nanoparticles (NPs) in combating the progress of HCC encouraged us to develop galactose-tailored PLGA NPs loaded with apigenin (API-GAL-NPs) for active liver targeting to treat HCC. Two kinds of apigenin NPs, such as apigenin-PLGA NPs (API-NPs) and API-GAL-NPs were fabricated and characterized by size, surface morphology, encapsulation efficacy, and in vitro drug release kinetics. In vitro assays were performed on HepG2 cells to check the cellular internalization, cytotoxic potential, and apoptotic potential of free apigenin (API), API-NPs, and API-GAL-NPs. In this stdy, API-GAL-NPs exhibited improved cellular internalization of API resulting in significantly high cytotoxic and apoptotic potentials to HepG2 cells over API and API-NPs. In in vivo studies, API-GAL-NPs exhibited a better protective effect against DEN-induced HCC in rats evidenced by the significant reduction of nodule formation, downregulation of matrix metalloproteinases (MMP-2 and MMP-9), and induction of apoptosis in the liver than API and API-NPs. Histopathological studies and scintigraphic imaging also confirmed that API-GAL-NPs treatment achieved better therapeutic efficacy against DEN-induced HCC in rats over API-NPs. In conclusion, API-GAL-NPs may serve as a potential therapeutic agent against HCC in the future by achieving improved liver targeting.
肝细胞癌 (HCC) 是全球最常见的肝脏恶性肿瘤。最近的一些报告集中在负载芹菜素的纳米粒子 (NPs) 在抗击 HCC 进展方面的疗效，这鼓励我们开发载有芹菜素的半乳糖化 PLGA NPs (API-GAL-NPs)，用于主动肝脏靶向治疗 HCC。两种类型的载有芹菜素的 NPs，如载有芹菜素的 PLGA NPs (API-NPs) 和 API-GAL-NPs，通过大小、表面形态、包封效率和体外药物释放动力学进行了表征。在 HepG2 细胞上进行了体外实验，以检查游离芹菜素 (API)、API-NPs 和 API-GAL-NPs 的细胞内摄取、细胞毒性和细胞凋亡潜力。在这项研究中，API-GAL-NPs 表现出对 API 的细胞内摄取的改善，导致对 HepG2 细胞的细胞毒性和细胞凋亡潜力明显高于 API 和 API-NPs。在体内研究中，API-GAL-NPs 对 DEN 诱导的大鼠 HCC 表现出更好的保护作用，表现在结节形成减少、基质金属蛋白酶 (MMP-2 和 MMP-9) 下调以及肝脏细胞凋亡增加，优于 API 和 API-NPs。组织病理学研究和闪烁成像也证实，API-GAL-NPs 治疗在 DEN 诱导的大鼠 HCC 方面比 API-NPs 取得了更好的治疗效果。总之，API-GAL-NPs 通过实现改善的肝脏靶向，可能成为未来治疗 HCC 的潜在治疗剂。
