科研之友
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摘要
In this study, a releasable disulfide carbonate linker is used to prepare disulfide-containing crosslinked polyethyleneimines (PEI-SS-CLs) for gene delivery. ESI-MS analysis shows that after being incubated with 1,4-dithio-DL-threitol (DTT), the degradable linkages in the polyethyleneimine (PEI) derivatives undergo disulfide bond cleavage followed by intramolecular cyclization and cleavage of the neighboring carbamate bond. Moreover, it is observed that thiol/polyanions trigger the release of DNA from polyplexes via the reductive degradability of PEI-SS-CLs and ion-exchange. In vitro transfection results indicate that PEI-SS-CL-1.5 (at a crosslinker/PEI feed molar ratio of 1.5) exhibits higher transfection efficacy than the commercially available reagents such as the high molecular weight PEI with a molecular weight of 25 kDa (PEI 25k) and the versatile liposomes Lipofectamine 2000. PEI-SS-CL-1.5 also demonstrates significantly lower cytotoxicity, compared with PEI 25k and Lipofectamine 2000. Our study indicates that incorporating the thiol-specific cleavable disulfide bond into crosslinked PEIs and implementing regulated release of DNA are effective strategies for designing safe and effective gene vectors.
