title: Transferrin-conjugated SNALPs encapsulating 2'-O-methylated miR-34a for the treatment of multiple myeloma.
abstract: Stable nucleic acid lipid vesicles (SNALPs) encapsulating miR-34a to treat multiple myeloma (MM) were developed. Wild type or completely 2'-O-methylated (OMet) MiR-34a was used in this study. Moreover, SNALPs were conjugated with transferrin (Tf) in order to target MM cells overexpressing transferrin receptors (TfRs). The type of miR-34a chemical backbone did not significantly affect the characteristics of SNALPs in terms of mean size, polydispersity index, and zeta potential, while the encapsulation of an OMet miR-34a resulted in a significant increase of miRNA encapsulation into the SNALPs. On the other hand, the chemical conjugation of SNALPs with Tf resulted in a significant decrease of the zeta potential, while size characteristics and miR-34a encapsulation into SNALPs were not significantly affected. In an experimental model of MM, all the animals treated with SNALPs encapsulating miR-34a showed a significant inhibition of the tumor growth. However, the use of SNALPs conjugated with Tf and encapsulating OMet miR-34a resulted in the highest increase of mice survival. These results may represent the proof of concept for the use of SNALPs encapsulating miR-34a for the treatment of MM.
authors.affiliation: Department of Pharmacy, Federico II University of Naples, Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Immacolata
authors.initials: I
authors.lastname: Scognamiglio
authors.affiliation: Department of Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100 Catanzaro, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Di Martino
authors.affiliation: Department of Pharmacy, Federico II University of Naples, Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Campani
authors.affiliation: Department of Pharmacy, Federico II University of Naples, Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Virgilio
authors.affiliation: Department of Pharmacy, Federico II University of Naples, Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Galeone
authors.affiliation: Department of Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100 Catanzaro, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Gullà
authors.affiliation: Department of Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100 Catanzaro, Italy.
authors.forename: Maria Eugenia
authors.initials: ME
authors.lastname: Gallo Cantafio
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Gabriella
authors.identifier: 0000-0002-7787-2531
authors.initials: G
authors.lastname: Misso
authors.affiliation: Department of Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100 Catanzaro, Italy.
authors.forename: Pierosandro
authors.initials: P
authors.lastname: Tagliaferri
authors.affiliation: Department of Medical Oncology, Department of Experimental and Clinical Medicine, Magna Graecia University and T. Campanella Cancer Center, Salvatore Venuta Campus, 88100 Catanzaro, Italy.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, 80138 Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Department of Pharmacy, Federico II University of Naples, Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Giuseppe
authors.identifier: 0000-0002-1210-1269
authors.initials: G
authors.lastname: De Rosa
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008745:Methylation; D016513:Mice, SCID; D035683:MicroRNAs / Q000378:metabolism*; D009101:Multiple Myeloma / Q000628:therapy*; D009696:Nucleic Acids / Q000737:chemistry*; D010316:Particle Size; D011990:Receptors, Transferrin / Q000378:metabolism; D055672:Static Electricity; D014168:Transferrin / Q000378:metabolism*; D053835:Unilamellar Liposomes / Q000737:chemistry*
chemical_list: D008055:Lipids; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D009696:Nucleic Acids; D011990:Receptors, Transferrin; D014168:Transferrin; D053835:Unilamellar Liposomes