期刊
BIOMACROMOLECULES
卷 18, 期 1, 页码 77-86出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.6b01378
关键词
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资金
- American Heart Association
- National Institutes of Health [F30 HL134255]
- National Science Foundation through a MRSEC award
- Biomolecular Materials program at the U.S. Department of Energy, Office of Basic Energy Science, Division of Materials Science [DE-SC0007063]
- U.S. Department of Energy (DOE) [DE-SC0007063] Funding Source: U.S. Department of Energy (DOE)
While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels that rapidly self-healed. With siRNA encapsulation, the assemblies eroded as polyplexes which were active and transfected cells, observed by Cy3-siRNA uptake or GFP silencing in vitro. When injected into rat myocardium, the hydrogels localized polyplex release, observed by uptake of Cy5.5-siRNA and silencing of GFP for 1 week in a GFP-expressing rat. These results illustrate the potential for this system to be applied for therapeutic siRNA delivery, such as in cardiac pathologies.
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