The application of the pillararene-based GSH depletion strategy in tumor therapy

Nowadays, depleting the intracellular glutathione (GSH) to improve the therapeutic efficacy of tumors is quite an appealing field. However, regardless of which strategy is adopted, one of the most crucial aspects is to precisely and efficiently deliver the GSH-depleting agents to the lesion locations. In addition, to demonstrate its value, the GSH depletion technology also needs to be combined with one or more therapeutic methods. Thus, an efficient drug delivery system (DDS) is particularly crucial in this therapeutic approach. Pillararenes, as emerging supramolecular tools, exhibit numerous unique features that make them very promising for DDSs, including structural flexibility, functionality richness, and assembly controllability. Pillararene-based nanodrugs can readily incorporate GSH-depleting agents due to the abundant modification sites and the excellent capacity for guest recognition of pillararenes. Over the past decade, pillararene-based GSH depletion tumor therapy technologies have shown a steep rise. In this short review, we outline the commonly employed GSH depletion strategy in pillararene-based nanodrugs for chemotherapy, photodynamic therapy, gasotransmitter-based therapy or their combined therapy towards tumors. At the end, some challenges in this field are also discussed to identify the directions that can be pursued for improvement. We hope that this thorough overview will inspire researchers to continue to delve deeper into this field and create more innovative and practical solutions for tumor treatment.