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Enzyme-responsive liposomes modified adenoviral vectors for enhanced tumor cell transduction and reduced immunogenicity

Paper ID Volume ID Publish Year Pages File Format Full-Text
6267 471 2013 11 PDF Available
Title
Enzyme-responsive liposomes modified adenoviral vectors for enhanced tumor cell transduction and reduced immunogenicity
Abstract

Limitations of adenoviral (Ad) vectors for cancer gene therapy could be overcome by their combination with pharmaceutical technologies. Here we show that an enzyme-responsive liposomal formulation could significantly enhance the tumor cell transduction abilities and reduce the immunogenicity of Ad vectors. In the current research, the enzymatically cleavable PEG-lipids composed of a PEG/matrix metalloproteinase (MMP)-substrate peptide/cholesterol (PPC) were synthesized and characterized by 1H NMR and TOF MS ES+. The obtained MMP-cleavable lipids were inserted into the anionic liposomal Ad vectors (AL-Ad) by the post-insertion method. The results of in vitro infection assays indicated that the enzymatically cleavable formulation (PPC-AL-Ad) displayed a much higher gene expression than naked Ad5 and the non-cleavable PEG-lipid modified Ad vectors in tumor cells. More importantly, PPC-AL-Ad induces a lower production of neutralizing antibody and lower innate immune response, as well as significantly reduced liver toxicity in vivo. These findings suggest that PPC-AL-Ad is a promising system for gene delivery in tumor therapy.

Keywords
Adenovirus; Anionic liposomes; PEG; Matrix metalloproteinase
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Enzyme-responsive liposomes modified adenoviral vectors for enhanced tumor cell transduction and reduced immunogenicity
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 12, April 2013, Pages 3020–3030
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us