Posted by Redox-responsive Methyl-β-cyclodextrin (MeβCD)-based supramolecular polyrotaxanes (MSPs) were fabricated: the amphiphilic diselenide-bridged axle polymer was loaded by MeβCD via the host-guest interaction and end-capped with two near-infrared (NIR) fluorescence probes IR783. The MSPs self-assemble with stimulators of interferon genes (STING) agonists diABZIs into nanoparticles (RDPNs@diABZIs), which enable simultaneous release of MeβCD and diABZIs in the redox tumor microenvironment. After the released diABZIs activate STING on antigen-presenting cells (APCs), de novo T-cell responses are initiated. Meanwhile, the released MeβCD depletes membrane cholesterol to overcome cancer-cell mechanical softness, which enhances the cytotoxic T lymphocytes (CTL)-mediated killing of cancer cells. In the female tumor-bearing mouse model, it is demonstrated that RDPNs@diABZIs lead to effective tumor regression and generate long-term immunological memory. Furthermore, RDPNs@diABZIs can achieve significant tumor eradication, with these mice remaining survival for at least 2 months.
Luo, H., Lv, J., Wen, P. et al. Supramolecular polyrotaxane-based nano-theranostics enable cancer-cell stiffening for enhanced T-cell-mediated anticancer immunotherapy. Nat Commun 16, 2331 (2025). https://doi.org/10.1038/s41467-025-57718-5