Incorporation of active DNA/cationic polymer polyplexes into hydrogel scaffolds.
The effective and sustained delivery of DNA and siRNAs locally would increase the applicability of gene therapy in tissue regeneration and cancer therapy. One promising approach is to use hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the disease sites. However, this approach is currently limited by the inability to load concentrated and active gene delivery nanoparticles into the hydrogels due to the severe nanoparticle aggregation during the loading process. Here, we present a process to load concentrated and un-aggregated non-viral gene delivery nanoparticles, using DNA/polyethylene imine (PEI) polyplexes as an example, into neutral polyethylene glycol (PEG), negatively charged hyaluronic acid (HA) and protein fibrin hydrogels crosslinked through various chemistries. The encapsulated polyplexes are highly active both in vitro and in vivo. We believe this process will significantly advance the applications of hydrogel scaffold mediated non-viral gene delivery in tissue regeneration and cancer therapy.
Lei
Yuguo
Y
Chemical and Biomolecular Engineering Department, University of California, Los Angeles, 420 Westwood Plaza, 5531 Boelter Hall, Los Angeles, CA 90095, USA.
Huang
Suxian
S
Sharif-Kashani
Pooria
P
Chen
Yong
Y
Kavehpour
Pirouz
P
Segura
Tatiana
T
D000818:Animals; D002412:Cations; D002417:Cattle; D002645:Chickens; D004247:DNA / Q000737:chemistry*; D005612:Freeze Drying; D018014:Gene Transfer Techniques; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D018919:Neovascularization, Physiologic; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry*; D054457:Tissue Scaffolds / Q000737:chemistry*
D002412:Cations; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA
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