Journal
NANOMEDICINE
Volume 11, Issue 15, Pages 1971-1991Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2016-0128
Keywords
lactic-co-glycolic acid; LGA-PEI polymer; nanoparticle; nucleic acid delivery; polyethylenimine; xenograft tumors
Funding
- Michael E DeBakey Department of Surgery
- Alkek Award from Baylor College of Medicine
- NIH [R01 CA183984]
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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.
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