PEG shielded MMP sensitive CPPs for efficient and tumor specific gene delivery in vivo
Number of Authors: 7
2015 (English)In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 209, 238-247 p.Article in journal (Refereed) Published
Gene therapy has great potential to treat a range of different diseases, such as cancer. For that therapeutic gene can be inserted into a plasmid vector and delivered specifically to tumor cells. The most frequently used applications utilize lipoplex and polyplex approaches where DNA is non-covalently condensed into nanoparticles. However, lack of in vivo efficacy is the major concern that hinders translation of such gene therapeutic applications into clinics. In this work we introduce a novel method for in vivo delivery of plasmid DNA (pDNA) and efficient tumor-specific gene induction using intravenous (i.v) administration route. To achieve this, we utilize a cell penetrating peptide (CPP), PepFect14 (PF14), double functionalized with polyethylene glycol (PEG) and a matrix metalloprotease (MMP) substrate. We show that this delivery vector effectively forms nanoparticles, where the condensed CPP and pDNA are shielded by the PEG, in an MMP-reversible manner. Administration of the complexes results in efficient induction of gene expression specifically in tumors, avoiding normal tissues. This strategy is a potent gene delivery platform that can be used for tumor-specific induction of a therapeutic gene.
Place, publisher, year, edition, pages
2015. Vol. 209, 238-247 p.
Gene delivery, Tumor, PEGylation, Cell-penetrating peptide, Non-covalent complexes, Matrix metalloprotease
Chemical Sciences Biological Sciences Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:su:diva-119123DOI: 10.1016/j.jconrel.2015.04.038ISI: 000355674300025OAI: oai:DiVA.org:su-119123DiVA: diva2:843813