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Title 

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

Authors 

J GeS H MinD M KimDong Chul LeeKyung Chan ParkYoung Il Yeom

Publisher 

Springer Verlag (Germany)

Issue Date 

2012

Citation 

Biotechnology and Bioprocess Engineering, vol. 17, no. 0, pp. 160-167

Keywords 

GelatinMetastatic tumorMMPPolyethylenimine (PEI)Targeting

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.

ISSN 

1226-8372

Link 

http://dx.doi.org/10.1007/s12257-011-0423-x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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