In present study, gene concentrated as well as bioreduction-ruptured
nanogel with local enrichment positive charge while low cytotoxicity was developed for Bcl2
siRNA delivery featured in intracellular switch on/off controlled release. Dynamic covalent bond crosslinked
nanogel was formed by thiolated PEI of 1.8 kDa(PEI-1.8 kDa)and biodegradable
dextrin. Once
nanogel was uptake by
tumor cells, high concentration of
glutathione (GSH) in cytosol could bioreducible -degrade and
rupture the crosslink of this
dextrin nanogel (DSP) into hypotoxic PEI-1.8 kDa and
dextrin, following by burst release of packed
siRNA and minimizing the restriction of
polymer material for
siRNA transcription. This switch on/off
siRNA release strategy for gene therapy exhibited equal level of the deregulation of Bcl2
protein expression determined by western blot analysis compared with cationic PEI with 25 kDa molecular weight (PEI-25 kDa) in vitro. Moreover, the gene concentrated DSP based on hypotoxic PEI-1.8 kDa and biodegradable
dextrin could be administrated intravenously for systematic
therapy on safely.
Tumor suppression study of DSP also exhibited a superior antitumor activity in 4T1-luc
tumor cell bearing BALB/C mice. Furthermore, it exhibited lower cytotoxicity, almost none hemotoxicity, moreover avoiding recognition and clearance by RES system in healthy mice. Overall, these findings suggest that this reduction-sensitive while bioreduction-ruptured
polymer nanogel is an innovative strategy and holds great promise for gene and drug delivery.