Liposomal delivery of nucleic acid-based anticancer therapeutics: BP-100-1.01

Ana Tari Ashizawa, Jorge Cortes

Research output: Contribution to journalReview article

19 Scopus citations

Abstract

Introduction: Antisense oligonucleotides, siRNA, anti-microRNA are designed to selectively bind to target mRNAs, and silence disease-causing or -associated proteins. The clinical development of nucleic acid drugs has been limited by their poor bioavailability.Areas covered: This review article examines the strategies that have been utilized to improve the bioavailability of nucleic acids. The chemical modifications made to nucleic acids that have improved their resistance against nuclease degradation are briefly discussed. The design of cationic and neutral lipid nanoparticles that enable the systemic delivery of nucleic acids in vivo is reviewed, and the proof-of-concept evidence that intravenous administration of nucleic acids incorporated into lipid nanoparticles leads to decreased expression of target genes in humans. Preclinical results of the neutral BP-100-1.01 nanoparticle are highlighted.Expert opinion: To further improve the clinical potential of nucleic acid cancer drugs, we predict research on the next generation of lipid nanoparticles will focus on: i) enhancing nucleic acid delivery to poorly vascularized tumors, as well as tumors behind the blood-brain barrier; and ii) improving the accessibility of nucleic acids to the cytoplasm by enhancing endosomal escape of nucleic acids and/or reducing exocytosis of nucleic acids to the external milieu.

Original languageEnglish (US)
Pages (from-to)1107-1120
Number of pages14
JournalExpert Opinion on Drug Delivery
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Keywords

  • Anti-microRNA
  • Antisense oligonucleotides
  • Cationic liposomes
  • Dioleoyl phosphatidylcholine
  • Drug delivery
  • Gene silencing
  • Growth factor receptor bound protein-2
  • Neutral liposomes
  • SiRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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