Overall, novel carrier-free, charge-reversal, nucleus-targeting, biodegradable, and DNA-affinity nanodrugs represent safe and effective platforms for the combination of CT and CDT.377078 Full cracked. An in vivo assessment further demonstrated the superior tumor selectivity and suppressor capacity and no/low toxicity of the nanodrugs. Finally, severe DNA damage induced mitochondrial apoptosis in HepG2 cells. Then, the dissociation of CMC-DD2 was efficiently triggered by intracellular hydrogen peroxide (H 2O 2) with the release of DNA damaging agents, including nitrate anions, hydroxyl radicals ( Nanodrugs internalized by the nucleus directly bound the DNA and altered its conformation. CMC-DD2 preferred to enter tumor cells and localize in the nucleus after lysosome escape due to its pH-dependent charge-reversal properties. To address this concern, novel carrier-free nanodrugs (CMC-DD2) self-assembled from the natural melanin complex (CMC) with a superior CDT performance, and dehydroabietic acid hexamer (DD2) displaying a potent antitumor activity were proposed for the synergistic combination of CT and CDT. The combination of chemotherapy (CT) and chemodynamic therapy (CDT) is an emerging therapeutic strategy for tumors however, its therapeutic efficacy is usually impaired by the shortage of high-efficiency intracellular catalysts for CDT and the poor tumor selectivity of CT.
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