Folate receptor-mediated intracellular delivery of recombinant caspase-3 for inducing apoptosis

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R ecombinant reversed caspase-3 (rev-caspase-3) is a pro-apoptotic gene capable of intracellular autocatalytic processing, which leads to programmed cell death. Folate receptor-specific intracellular delivery of the rev-caspase-3 gene into KB cells overexpressing folate receptors was explored by employing the folate-poly(ethylene glycol)-polyethylenimine (FOL-PEG-PEI) conjugate as a nonviral polymeric carrier. Using luciferase as a reporter gene, the conditions for formulation of DNA/polymer polyplexes were pre-optimized to attain the highest folate receptor-mediated gene transfection efficiency. FOL-PEG-PEI conjugate complexed with rev-caspase-3 plasmid in an optimized condition gave rise to a great increase in expression and activation of exogenous rev-caspase-3 in KB cells when pretreated with doxorubicin. The synthesized conjugate exhibited higher transfection efficiency than other commercially available transfection agents due to a unique mechanism of folate-receptor mediated endocytic gene transfer. The transfected cells showed a significant extent of apoptosis by rev-caspase-3. This study suggests the potential of using folate-receptor-mediated delivery of rev-caspase-3 gene for inducing tumor cell death in a target-specific manner. (c) 2005 Elsevier B.V All rights reserved.
Publisher
ELSEVIER SCIENCE BV
Issue Date
2005-11
Language
English
Article Type
Article
Keywords

GENE DELIVERY; CATIONIC POLYMERS; PLASMID DNA; CELLS; CANCER; POLYETHYLENIMINE; BINDING; GA-67-DEFEROXAMINE-FOLATE; EXPRESSION; COMPLEXES

Citation

JOURNAL OF CONTROLLED RELEASE, v.108, no.1, pp.121 - 131

ISSN
0168-3659
DOI
10.1016/j.jconrel.2005.07.015
URI
http://hdl.handle.net/10203/12414
Appears in Collection
NT-Journal Papers(저널논문)BS-Journal Papers(저널논문)
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