Supramolecular self-assemblies based on water-soluble pillar[6]arene and drug-drug conjugates for the combination of chemotherapy

Although some co-drug delivery systems have been reported to treat cancer, how to optimal design these nano-systems with enhanced therapeutic efficacy is still a major challenge. As for the nitrogen mustard drugs chlorambucil (Cb), the overexpressed glutathione (GSH) in cancer tissue is responsible for their detoxification and reduced bioavailability. In this paper, chlorambucil-oxoplatin (Cb-Pt) was prepared to fabricate water-soluble pillar[6]arene (WP[6]) based supramolecular drug-drug self-assemblies (SDSAs). Remarkably, after the transcytosis by cancer cells, SDSAs was reduced by GSH to re lease Cb and higher toxic cisplatin, accompanying with the declining GSH level and ascending ROS level. Moreover, in vitro and in vivo experiments demonstrated that SDSAs with oxidative stress amplification strategy exhibited excellent therapeutic effect. This strategy might be useful for the synergistic co-drug based chemotherapy field. • Supramolecular drug-drug self-assemblies are constructed for chemotherapy. • Host-guest interactions based stimuli-responsive nano systems were prepared. • The down-regulation of GSH could enhance the chemotherapeutic efficiency.