Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the treatment of multiple myeloma

Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed.Wild type orcompletely 2-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) inorder to targetMMcells overexpressing transferrin receptors (TfRs).The type of miR-34a chemical backbone did not significantlyaffect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation ofan OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemicalconjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34aencapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPsencapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf andencapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept forthe use of SNALPs encapsulating miR-34a for the treatment of MM.