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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 t1/2 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.
Highlights
Cervical cancer is one of the major world problems and considered to be one of the common gynecologic cancers making it as fourth most cancer related death among women (Kanavos 2006)
In this study, we have selected miR-1284 to increase the chemosensitivity of CDDP for the treatment of cervical cancers (Huang et al 2017; Pan et al 2016)
Preparation of CD59sp‐conjugated CDDP/miRNA‐loaded liposomes At first, CDDP-loaded liposome was prepared by hydration-sonication method
Summary
Cervical cancer is one of the major world problems and considered to be one of the common gynecologic cancers making it as fourth most cancer related death among women (Kanavos 2006). Several of the miRNAs are indicated as key regulators in the proliferation, differentiation and regulation of cancer cell growth by acting on the gene expression at posttranscriptional level (Shin and Chu 2014). Studies have demonstrated that miRNAs can exhibit the control over cancer cells by controlling the key pathways (Ramasamy et al 2019). In this regard, miR-1284 has been shown to inhibit the cancer cell growth by targeting the downstream targets (Li et al 2017). In this study, we have selected miR-1284 to increase the chemosensitivity of CDDP for the treatment of cervical cancers (Huang et al 2017; Pan et al 2016)
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