Selective gene delivery to cancer cells secreting matrix metalloproteinases using a gelatin/polyethylenimine/DNA complex

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Title
Selective gene delivery to cancer cells secreting matrix metalloproteinases using a gelatin/polyethylenimine/DNA complex
Author(s)
J Ge; S H Min; D M Kim; Dong Chul LeeKyung Chan ParkYoung Il Yeom
Bibliographic Citation
Biotechnology and Bioprocess Engineering, vol. 17, pp. 160-167
Publication Year
2012
Abstract
We developed a gene delivery strategy targeting metastatic tumors by exploiting the specific matrix metalloproteinases (MMPs) secreting properties of metastatic tumor cells. A ternary polyplex has been formed by coating polyethylenimine/DNA (PD) complex with an excessive amount of negatively charged gelatin B (GPDB). We show that GPD-B's gene delivery activity could be targeted to cancer cells via the MMP-mediated proteolytic process, while GPD-A, made from positively charged gelatin A, was not successful in exhibiting such activity. The 1, 10-Phenanthroline, an MMP2 inhibitor, abrogated the MMPdependent transfection activity of GPD-B. GPD-B carried much less positive surface charges than PD, and thus exhibited significantly reduced interactions with erythrocytes. However, MMP2 elevated the positiveness in GPDB's surface charge and, thus, its interaction with erythrocytes. These results suggest that the anionic gelatin coating may confer improved stabilities on GPD-B in the surrounding medium, while MMP2-mediated disintegration of the gelatin coat enhances the gene delivery to metastatic cancer cells via increasing the likelihood of local chargemediated interactions between the polyplex and cancer cell membrane.
Keyword
GelatinMetastatic tumorMMPPolyethylenimine (PEI)Targeting
ISSN
1226-8372
Publisher
South Korea
DOI
http://dx.doi.org/10.1007/s12257-011-0423-x
Type
Article
Appears in Collections:
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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