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

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Recombinant 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 over-expressing 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.
Publisher
Elsevier
Issue Date
2005-11-02
Keywords

PEI; folate; Receptor-mediated endocytosis; Rev-caspase-3; Apoptosis

Citation

Journal of Controlled Release, Vol.108, No.1, pp.121-131

ISSN
0168-3659
DOI
10.1016/j.jconrel.2005.07.015
URI
http://hdl.handle.net/10203/14367
Appears in Collection
BS-Conference Papers(학술회의논문)

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