Wang Li, Liang Ting-Ting
Department of Pharmacy, Jining No. 1, People's Hospital, Jining, 272011, Shandong, China.
Department of Obstetrics and Gynecology, Weifang No. 2 People's Hospital, No. 7 Yuanxiao Street, Kuiwen District, Weifang, 261041, Shandong, China.
AMB Express. 2020 Mar 17;10(1):54. doi: 10.1186/s13568-020-00990-z.
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 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 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.
在单一纳米载体中将两种不同的治疗剂（miRNA - 1284和顺铂（CDDP））共同递送至癌细胞为癌症治疗提供了新的维度。在本研究中，我们设计了负载CD59sp共轭miRNA - 1284/顺铂（CDDP）的脂质体，以增强对宫颈癌的治疗效果。与负载miRNA - 1284/CDDP的脂质体（LP - miCDDP）相比，CD59抗体共轭的LP - miCDDP（CD/LP - miCDDP）在HeLa细胞中显示出显著更高的细胞毒性。值得注意的是，由于HMGB1的下调，MiR - 1284在宫颈癌细胞中显示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（约20%）或miR - 1284（约12%）处理的细胞相比，CD/LP - miCDDP导致最大的凋亡效应（约60%），表明其在癌细胞中具有优异的抗癌效果。重要的是，CD/LP - miCDDP显著延长了包封药物在大鼠体内的血液循环，CD/LP - miCDDP的AUC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）降低了八倍，t增加了3.6倍。总体而言，结果表明治疗成分的靶向和协同共同递送在宫颈癌治疗中可能具有前景。
