New polymer of lactic-co-glycolic acid-modified polyethylenimine for nucleic acid delivery

Nanomedicine (Lond). 2016 Aug;11(15):1971-91. doi: 10.2217/nnm-2016-0128. Epub 2016 Jul 26.

Abstract

Aim: To develop an improved delivery system for nucleic acids.

Materials & methods: We designed, synthesized and characterized a new polymer of lactic-co-glycolic acid-modified polyethylenimine (LGA-PEI). Functions of LGA-PEI polymer were determined.

Results: The new LGA-PEI polymer spontaneously formed nanoparticles (NPs) with DNA or RNA, and showed higher DNA or RNA loading efficiency, higher or comparable transfection efficacy, and lower cytotoxicity in several cell types including PANC-1, Jurkat and HEK293 cells, when compared with lipofectamine 2000, branched or linear PEI (25 kDa). In nude mouse models, LGA-PEI showed higher delivery efficiency of plasmid DNA or miRNA mimic into pancreatic and ovarian xenograft tumors. LGA-PEI/DNA NPs showed much lower toxicity than control PEI NPs in mouse models.

Conclusion: The new LGA-PEI polymer is a safer and more effective system to deliver DNA or RNA than PEI.

Keywords: LGA-PEI polymer; lactic-co-glycolic acid; nanoparticle; nucleic acid delivery; polyethylenimine; xenograft tumors.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • DNA / administration & dosage
  • DNA / chemistry
  • Female
  • Genetic Therapy / methods*
  • HEK293 Cells
  • Humans
  • Lactic Acid / chemistry*
  • Mice
  • Mice, Nude
  • Nanoparticles
  • Nucleic Acids / administration & dosage*
  • Nucleic Acids / chemistry*
  • Ovarian Neoplasms / drug therapy
  • Pancreatic Neoplasms / drug therapy
  • Particle Size
  • Plasmids
  • Polyethyleneimine / chemistry*
  • Polyethyleneimine / pharmacology
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • RNA / administration & dosage
  • RNA / chemistry
  • Transfection

Substances

  • Nucleic Acids
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • RNA
  • Polyethyleneimine
  • DNA