Nitric oxide-containing supramolecular polypeptide nanomedicine based on [2]biphenyl-extended-pillar[6]arenes for drug resistance reversal

A kind of supramolecular polypeptide nanomedicine (BPC/DOX-ICG) was constructed with an anionic water-soluble [2]biphenyl-extended-pillar[6]arene (AWBpP6), and pyridinium-terminal- and S-nitrosothiol (SNO)-modified polypeptide (PPNC) via host-guest interactions to co-deliver doxorubicin (DOX) and indocyanine green (ICG) for drug resistance reversal. Upon near-infrared (NIR) irradiation, the NO generation could down-regulate the P-glycoprotein (P-gp) expression level to reverse multidrug resistance (MDR). Subsequently, the resulting reverse MDR could sensitize the free DOX and assist photothermal therapy (PTT) to enhance the tumoricidal potential. This supramolecular polypeptide nanomedicine provides an effective strategy for the multimodal synergistic therapies of photothermal therapy, NO generation therapy, and chemotherapy (i.e., PTT-NO-CT) to overcome MDR.