Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, Zhengzhou 450001, China.
Nanoscale. 2017 Jun 1;9(21):7284-7296. doi: 10.1039/c7nr01350g.
Numerous studies have demonstrated that microRNAs are very important in cancer development and progression. However, the complex relationship between the size of microRNA delivery systems, cellular uptake, biodistribution and therapeutic efficiency remains unclear. Herein, we have successfully constructed a series of differently-sized microRNA delivery systems, miR-26a-loaded, hyaluronic acid-modified, polyetherimide-conjugated PEGylated gold nanocage ternary nanocomplexes (PPHAuNCs-TNCs), which can be monitored optically by fluorescence and photoacoustic tomography imaging. We evaluated the effect of the particle size on the cellular uptake and biodistribution in the BEL-7402 cell line in vitro and in the subcutaneous and orthotopic hepatocellular carcinoma (HCC) mouse models. Our findings showed that the cellular uptake and biodistribution were optimal for cancer therapy with the PPHAuNCs-30-TNCs (30 nm AuNCs in edge length) in comparison with their 50 nm and 70 nm counterparts. PPHAuNCs-30-TNCs could accumulate in the liver for a longer time in an orthotopic mouse model of HCC than that in normal mice and could considerably restrain tumor growth in an orthotopic HCC mouse model under near-infrared radiation. This study may provide insightful information for developing novel non-viral microRNA vectors, and PPHAuNCs-30-TNCs have great potential for application in tumor diagnosis and cancer therapy in the future.
大量研究表明，microRNAs 在癌症的发生和发展中非常重要。然而，microRNA 递药系统的大小、细胞摄取、体内分布和治疗效率之间的复杂关系仍不清楚。在此，我们成功构建了一系列不同大小的 microRNA 递药系统，即负载 miR-26a、透明质酸修饰、聚醚酰亚胺偶联聚乙二醇化金纳米笼三元纳米复合物（PPHAuNCs-TNCs），可通过荧光和光声断层扫描成像进行光学监测。我们评估了粒径对 BEL-7402 细胞系体外和皮下及原位肝癌（HCC）小鼠模型中细胞摄取和体内分布的影响。研究结果表明，与 50nm 和 70nm 相比，PPHAuNCs-30-TNCs（边长 30nm 的 AuNCs）在细胞摄取和体内分布方面对癌症治疗更有利。PPHAuNCs-30-TNCs 能够在原位 HCC 小鼠模型中在肝脏中更长时间地积累，并且在近红外辐射下能够显著抑制原位 HCC 小鼠模型中的肿瘤生长。这项研究可为开发新型非病毒 microRNA 载体提供有价值的信息，PPHAuNCs-30-TNCs 具有在肿瘤诊断和癌症治疗方面的巨大应用潜力。
