KMID : 1094720120170010160
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Biotechnology and Bioprocess Engineering 2012 Volume.17 No. 1 p.160 ~ p.167
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Selective gene delivery to cancer cells secreting matrix metalloproteinases using a gelatin/polyethylenimine/DNA complex
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Ge Jiang
Min Sang-Hyun Kim Dong-Min Lee Dong-Chul Park Kyung-Chan Yeom Young-Il
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Abstract
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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 MMP-dependent 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.
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KEYWORD
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gelatin, MMP, metastatic tumor, targeting, polyethylenimine (PEI)
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