PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma.
PLGA-based dual targeted nanoparticles enhance miRNA transfection efficiency in hepatic carcinoma.
复制标题
基于 PLGA 的双靶向纳米颗粒提高肝癌中 miRNA 转染效率
DOI：
10.1038/srep46250
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发表时间：
2017-04-07
影响因子：
4.6
通讯作者：
Liu P
中科院分区：
文献类型：
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作者：
Cai C;Xie Y;Wu L;Chen X;Liu H;Zhou Y;Zou H;Liu D;Zhao Y;Kong X;Liu P
肝癌（Hepatic carcinoma，HCC）是一种发病率高、预后差的致死性疾病.近年来，基因治疗为改善肝癌患者的预后提供了新的方法。MicroRNA-99 a（miR-99 a）在HCC中经常下调，在那里它作为肿瘤抑制因子。因此，我们构建了单甲氧基聚乙二醇（D，L-丙交酯-共-乙交酯）-聚（L-赖氨酸）-乳糖酸-抗血管内皮生长因子抗体本发明提供了具有高度特异性靶向性质的纳米颗粒（mPEG-PLGA-PLL-LA/VEGFab或PEAL-LA/VEGFab）作为载体，以恢复miR-99 a在体外和体内的表达，从而抑制HCC进展。PEAL-LA/VEGFab NP显示出比常规转染试剂LipofectamineTM 2000（Lip 2000）更有效地将miR-99 a递送至HepG 2细胞。PEAL-LA/VEGFab NPs的高递送效率导致靶基因表达下调，抑制HepG 2细胞的增殖、迁移和侵袭，体内实验表明，miR-99 a-PEAL-LA/VEGFab NPs可抑制肝癌移植瘤的生长，但无明显的全身毒性。我们的研究结果表明，PEAL-LA/VEGFab NPs基于这些纳米颗粒的双靶向特性，选择性地有效地将miR-99 a递送到HCC细胞，从而为转化为有效的HCC临床疗法提供了潜力。
Hepatic carcinoma (HCC) is a lethal disease associated with high morbidity and poor prognosis. Recently years, gene therapies have offered novel modalities to improve the prognosis of HCC patients. MicroRNA-99a (miR-99a) is frequently down-regulated in HCC, where it acts as a tumor suppressor. Therefore, we constructed monomethoxy (polyethylene glycol)-poly(D,L-lactide-co-glycolide)-poly(L-lysine)-lactobionic acid- anti-vascular endothelial growth factor antibody (mPEG-PLGA-PLL-LA/VEGFab or PEAL-LA/VEGFab) nanoparticles (NPs) with highly specific targeting properties as carriers to restore the expression of miR-99a bothin vitroandin vivo, to inhibit HCC progression.In vitro, PEAL-LA/VEGFab NPs showed more efficient delivery of miR-99a to HepG2 cells than the conventional transfection reagent LipofectamineTM2000 (Lip2000). The higher delivery efficiency associated with PEAL-LA/VEGFab NPs consequently resulted in down-regulation of target genes and suppression of the proliferation, migration and invasion of HepG2 cells.In vivo, miR-99a-PEAL-LA/VEGFab NPs inhibited tumor xenograft growth in HCC-bearing mice without causing obvious systemic toxicity. Our results demonstrate that PEAL-LA/VEGFab NPs selectively and effectively deliver miR-99a to HCC cells based on the double-targeting character of these nanoparticles, thereby offering potential for translation into effective clinical therapies for HCC.