Abstract

Co-delivery of two different therapeutics (miRNA-1284 and cisplatin (CDDP)) into the cancer cells in a single nanocarrier provides new dimension to the cancer treatment. In this study, we have designed the CD59sp-conjugated miRNA-1284/cisplatin(CDDP)-loaded liposomes for the enhanced therapeutic effect against cervical cancers. Compared with miRNA-1284/CDDP-loaded liposomes (LP-miCDDP), CD59 antibody-conjugated LP-miCDDP (CD/LP-miCDDP) showed a significantly higher cytotoxicity in HeLa cells. Notably, MiR-1284 showed a typical concentration-dependent cell killing effect in the cervical cancer cells owing to the downregulation of HMGB1. Flow cytometer analysis showed that CD/LP-miCDDP resulted in maximum apoptosis effect (~ 60%) compared to CDDP (~ 20%) or miR-1284 (~ 12%) treated cells indicating the superior anticancer effect in the cancer cells. Importantly, CD/LP-miCDDP significantly prolonged the blood circulation of encapsulated drug in rats with AUC_(o-t) of CD/LP-miCDDP showed a 6.9 fold higher value than that of free CDDP. Similarly, CD/LP-miCDDP showed an eightfold decrease in the clearance (CL) and 3.6-fold higher t_1/2 compared to that of free CDDP. Overall, results demonstrated that targeted and synergistic co-delivery of therapeutic components could be promising in cervical cancer therapy.

中文翻译：

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CD59受体靶向递送miRNA-1284和顺铂脂质体可有效抵抗宫颈癌细胞

摘要

在单个纳米载体中将两种不同的治疗剂（miRNA-1284和顺铂（CDDP））共同递送到癌细胞中为癌症治疗提供了新的方向。在这项研究中，我们设计了结合CD59sp的miRNA-1284 /顺铂（CDDP）脂质体，以增强对宫颈癌的治疗效果。与装载miRNA-1284 / CDDP的脂质体（LP-miCDDP）相比，结合CD59抗体的LP-miCDDP（CD / LP-miCDDP）在HeLa细胞中显示出更高的细胞毒性。值得注意的是，由于HMGB1的下调，MiR-1284在宫颈癌细胞中表现出典型的浓度依赖性细胞杀伤作用。流式细胞仪分析表明，与CDDP（〜20％）或miR-1284（〜12％）处理的细胞相比，CD / LP-miCDDP导致最大的细胞凋亡效应（〜60％），表明在癌细胞中具有优越的抗癌作用。CD / LP-miCDDP的_（ot）值比游离CDDP高6.9倍。同样，与游离CDDP相比，CD / LP-miCDDP的清除率（CL）降低了8倍，t _1/2升高了3.6倍。总体而言，结果表明治疗成分的靶向性和协同共递送在宫颈癌治疗中可能很有希望。