Microfluidic-synthesized anticancer peptide loaded bimetallic MOF complexes enhance tumor immunotherapy via pyroptosis

Pyroptosis immunotherapy has shown great potential in cancer treatment, but its clinical application is often hindered by insufficient immune activation and low bioavailability. Here, we report a bimetallic MOF-based nanoplatform (At10@CoZn-MOF) constructed via a microfluidic device to encapsulate the anticancer peptide (ACP) At10 within a Co/Zn-MOF framework. The nanosystem exhibits excellent physicochemical stability, pH-responsive drug release, and efficient cellular uptake. Notably, At10@CoZn-MOF possesses Fenton-like catalytic activity and, in combination with At10-induced mitochondrial damage, efficiently generates reactive oxygen species (ROS), which ultimately activates the caspase-1/GSDMD pathway, mediating pyroptosis and inducing immunogenic cell death. Importantly, At10@CoZn-MOF evokes robust pyroptotic responses in vivo, leading to tumor cell death and strong antitumor immunity. Taken together, the robust microfluidic synthesis of At10@CoZn-MOF provides an effective strategy for pyroptosis-mediated cancer therapy.