CD59 receptor targeted delivery of miRNA-1284 and Cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancers

Abstract

Background: In this study, we have designed the CD59sp-conjugated miRNA-1284/cisplatin(CDDP)-loaded liposomes for the enhanced therapeutic effect against cervical cancers. Methods: A substantially higher uptake of CD59 antibody-conjugated miRNA-1284/CDDP-loaded liposomes (CD/LP-miCDDP) was attributed to the CD59-based receptor-mediated cellular internalization in HeLa cells. Results: MiR-1284 showed a typical concentration-dependent cell killing effect in the cervical cancer cells owing to the downregulation of HMGB1. CD59-antibody conjugated formulation exhibited a significantly lower cell viability compared to that of free CDDP and non-targeted LP-miCDDP. The combination of miR-1284 and CDDP could result in a synergistic anticancer effect on the cervical cancer cells. The IC50 value of CDDP, LP-miCDDP and CD/LP-miCDDP was observed to be 12.4 µg/ml, 7.23 µg/ml and 3.12 µg/ml, respectively. CD/LP-miCDDP exhibited remarkable cell/nuclei rupturing and apoptotic bodies’ formation indicating a severe apoptosis effect in HeLa cancer cells. 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. Conclusions: Finally, CD/LP-miCDDP significantly prolonged the blood circulation of encapsulated drug in rats with significantly higher AUC (o-t) , t 1/2 and lower CL compared to that of free CDDP. Overall, CD/LP-miCDDP could hold a promising potential in the treatment of cervical cancers.