Topological Quantum Biomaterials Enable Pyroptosis-Senescence Coupling for Enhanced Colorectal Cancer Therapy

Inducing pyroptosis in tumor cells has emerged as a promising anticancer strategy. However, under sublethal oxidative stress, a considerable fraction of cancer cells evades pyroptosis and undergoes therapy-induced senescence, which ultimately drives chronic inflammation and facilitates tumor relapse. Here, we report an ultrasound-responsive sequential therapeutic strategy that orchestrates the pyroptosis-senescence axis for improved colorectal cancer therapy. This sequential therapeutic strategy integrates two functional modules, including morphologically engineered Pd₃Sn topological quantum biomaterials and senolytic agent piperlongumine. Upon ultrasound irradiation, the tailored Pd₃Sn nanostructures generate reactive oxygen species, which subsequently trigger zDHHC5-mediated S-acylation of gasdermin D, thereby initiating pyroptosis in colorectal cancer cells. Benefiting from its facet dependent near Fermi level electronic states and favorable peroxide activation kinetics, Pd₃Sn achieves substantially improved sonocatalytic performance, allowing for the controlled production of radicals and the accurate triggering of the pyroptosis cascade. Intriguingly, the senescence-associated secretory phenotype factors released from pyroptotic cells drive the surviving cancer cells into a senescent state. These senescent cells are then selectively eliminated by piperlongumine, effectively abrogating their senescence-associated pro-tumorigenic effects. In subcutaneous and liver metastasis models, this nanoplatform significantly suppresses tumor progression, achieving an 83.4% tumor volume inhibition rate and minimal liver metastatic burden. This work opens the application of quantum biomaterials in biomedicine and establishes a new therapeutic paradigm for disease treatment.