Pillar[6]arene-based supramolecular self-assemblies for two-pronged GSH-consumption-augmented chemo/photothermal therapy
Yang Bai, Xihua Li, Sijie Song, Jing Yang, Xia Liu, Zhaowei Chen
Abstract
The abundant intracellular glutathione (GSH) in cancer cells severely undermines the therapeutic efficacy of different treatments due to their role in protecting cancer cells from the associated oxidative stress. Developing a highly integrated system to consume GSH would help to improve the therapeutic outcomes. In this study, supramolecular prodrug self-assemblies (SPSAs) with IR825 loaded inside were developed to consume GSH via two-pronged pathways while augmenting the therapeutic potency of chemo/photothermal treatment. SPSAs were prepared using water-soluble pillar[6]arene (WP[6]) as host units and H2O2-responsive nitrogen mustard prodrug, chlorambucil-(phenylboronic acid pinacol ester) conjugates (Cb-BE), as the guests. When SPSAs were internalized by cancer cells, the generation of quinone methide (QM) from Cb-BE and singlet oxygen (1O2) from irradiation-activated IR825 could consume GSH in a concerted way. As such, the therapeutic efficacies of the released chlorambucil and the accompanied hyperthermia were augmented toward synergistically inhibiting tumor growth.