Cascaded amplification of intracellular oxidative stress and reversion of multidrug resistance by nitric oxide prodrug based-supramolecular hydrogel for synergistic cancer chemotherapy

摘要

Chemotherapy is the traditional treatment for clinical cancer patient [1,2]. However, the therapeutic effect is often severely limited by the multidrug resistance (MDR) [3,4], which was commonly mediated by inactivating drugs, increasing efflux, stimulating DNA repair mechanisms, and/or activating detoxification pathways [5–7]. Recent studies are committing to develop reasonable strategies for intervention of the molecular pathways mediating MDR, of which P-glycoprotein (P-gp) has been widely investigated [8]. So far, several kinds of P-gp inhibitors, including verapamil [9],vitamin E [10], cyclosporin A [11], and small interfering RNA (siRNA) [12], have been used to increase the intracellular accumulation of chemotherapeutic drugs. However, there is still a vigorous requirement to develop novel bioactive inhibitors, which could not only decrease the expression of P-gp thus increasing the intracellular accumulation of antitumor drugs, but also have effective tumor inhibition effect by its-self.