期刊
MOLECULAR THERAPY
卷 20, 期 3, 页码 601-608出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mt.2011.267
关键词
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资金
- NIH [HL63034, HL091478, R21EB007244, P01HL69779]
- Beckman Young Investigator Award
- Alfred P. Sloan Fellowship
- National Science Foundation
- University of Cincinnati College of Medicine
- University of Cincinnati Institute for Nanoscale Science and Technology
Using a new class of nontoxic and degradable glycopolymer-based vehicles termed poly(glycoamidoamine)s, we demonstrate virus-like delivery efficacy of oligodeoxynucleotide (ODN) decoys to cardiomyoblasts (H9c2), primary cardiomyocytes, and the mouse heart. These glycopolymers bind and compact ODN decoys into nanoparticle complexes that are internalized by the cell membrane and mediate nuclear uptake of DNA in 90+% of cultured primary cardiomyocytes and 87% of the mouse myocardium. Experimental results reveal that decoys delivered via these glycopolymers block the activation of the transcription factor NF-kappa B, a major contributor to -ischemia/reperfusion injury. Decoy complexes formed with glycopolymer T4 significantly blocked downstream gene expression of Cox-2 and limited myocardial infarction in vivo, phenocopying a transgenic mouse model. These promising delivery vehicles may facilitate high-throughput genetic approaches in animal models. Additionally, the low toxicity, biodegradation, and outstanding delivery efficacy suggest that these nanomedicines may be clinically applicable for gene regulatory therapy. Received 9 June 2011; accepted 12 November 2011; published online 20 December 2011. doi:10.1038/mt.2011.267
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