Journal
MACROMOLECULAR RESEARCH
Volume 29, Issue 9, Pages 636-647Publisher
POLYMER SOC KOREA
DOI: 10.1007/s13233-021-9078-4
Keywords
nonviral vector; polyamidoamine (PAMAM) dendrimer; cathepsin B; FKFL; transfection
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Funding
- Chungnam National University
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By using a bioreducible polymer as a nonviral vector and introducing enzyme-cleavable linkers and dipeptides, researchers achieved high transfection efficiency and low cytotoxicity in overexpressing cathepsin B cells. This study suggests that a combination of enzyme- and reduction-responsive linkers can improve the drawbacks associated with nonviral vectors in gene medicine.
Nonviral vectors have the potential for gene delivery comparable to viral vectors given their productive and economic advantages. However, the low transfection efficiency and specificity of nonviral vectors limit their application in gene medicine. To increase specificity, we selected cystamine core polyamidoamine (PAMAM) generation 3 (cPAMAM G3), a bioreducible polymer, and synthesized the FKFL sequence, as a cathepsin B-cleavable linker to cPAMAM G3. In addition, we simultaneously introduced RH dipeptides to FKFL-cPAMAM G3 to improve transfection efficiency. The synthesized RHFKFL-cPAMAM G3 showed similar transfection efficiency and low cytotoxicity compared with that of PEI 25 kDa in HepG2 and SW480 cells, which are cathepsin B enzyme overexpression cell lines. These results imply that a combination of enzyme- and reduction-responsive linkers can be used to solve the problems associated with the use of nonviral vectors.
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