Selective gene delivery to cancer cells secreting matrix metalloproteinases using a gelatin/polyethylenimine/DNA complex |
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Authors: | Jiang Ge Sang-Hyun Min Dong Min Kim Dong Chul Lee Kyung Chan Park Young Il Yeom |
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Institution: | 1.Medical Genomics Research Center,Korea Research Institute of Bioscience and Biotechnology,Daejeon,Korea;2.Bioengineering College,Dalian University,Dalian,China |
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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 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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