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

1.Introduction 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].