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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.
AuthorsDonato Cosco, Felisa Cilurzo, Jessica Maiuolo, Cinzia Federico, Maria Teresa Di Martino, Maria Chiara Cristiano, Pierfrancesco Tassone, Massimo Fresta, Donatella Paolino
JournalScientific reports (Sci Rep) Vol. 5 Pg. 17579 (Dec 01 2015) ISSN: 2045-2322 [Electronic] England
PMID26620594 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • MIRN34 microRNA, human
  • MicroRNAs
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Chitosan
Topics
  • Animals
  • Antineoplastic Agents (chemistry, pharmacology)
  • Chitosan (chemistry, pharmacology)
  • Drug Carriers (chemistry, pharmacology)
  • Humans
  • Lactic Acid (chemistry, pharmacology)
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs (chemistry, pharmacology)
  • Multiple Myeloma (drug therapy, metabolism, pathology)
  • Nanoparticles (chemistry)
  • Polyglycolic Acid (chemistry, pharmacology)
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Xenograft Model Antitumor Assays

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