title: Delivery of miR-34a by chitosan/PLGA nanoplexes for the anticancer treatment of multiple myeloma.
abstract: The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.|IRC FSH- Interregional Research Center for Food Safety &Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto; Catanzaro, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Cosco
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Felisa
authors.initials: F
authors.lastname: Cilurzo
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Jessica
authors.initials: J
authors.lastname: Maiuolo
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Federico
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Di Martino
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Cristiano
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, US.
authors.forename: Pierfrancesco
authors.initials: P
authors.lastname: Tassone
authors.affiliation: Department of Health Sciences, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.|IRC FSH- Interregional Research Center for Food Safety &Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto; Catanzaro, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fresta
authors.affiliation: Department of Experimental and Clinical Medicine, University "Magna Græcia" of Catanzaro, Campus Universitario "S. Venuta", Viale S. Venuta, Germaneto, I-88100 Catanzaro, Italy.|IRC FSH- Interregional Research Center for Food Safety &Health, University of Catanzaro "Magna Græcia", Campus Universitario "S. Venuta" - Building of BioSciences, Viale S. Venuta, I-88100 Germaneto; Catanzaro, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Paolino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D035683:MicroRNAs / Q000737:chemistry / Q000494:pharmacology; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan