Bioreducible ε-poly(<SUB>L</SUB>-lysine) nanogels for intracellular drug delivery
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초록
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To effective encapsulate and intracellularly release payloads, this study designed ε-poly(L-lysine) (EPL)-based bioreducible nanogels (REPL NGs) with multiple disulfide bonds because of intrinsic endosomolytic and nuclear importing functions of EPL. The resultant REPL NGs had about 10 nm in diameter and almost neutral zeta-potentials. In HCT116 cells, their cytotoxicity at ＜ 60 μg/mL was negligible. Doxorubicin-loaded REPL NGs (DOX@REPL NGs) with approximately 30 nm in diameter and positive zeta-potentials showed about 3-10-fold better cell-killing effects than free DOX in HCT116 cells. In HCT116 tumor-bearing mice, DOX@REPL NGs made more potent tumor growth inhibition than free DOX‧HCl. In conclusion, the designed pH and thiol dual stimuli-sensitive REPL NGs could be potential drug carriers for effective intracellular delivery of hydrophobic chemical drugs.