MXene-based dual-gated multifunctional nanodrug induced ferroptosis and modulated tumor microenvironment to treat pancreatic cancer

The inhibitory immune microenvironment of pancreatic cancer prevents the infiltration and activation of antitumor immune cells. Therefore, breaking the barrier of pancreatic cancer immune microenvironment is the key to activate antitumor immunity, but there is still no effective method reported so far. Immunogenic cell death (ICD) of tumor cells is considered to be an effective method to activate antitumor immunity. Accordingly, we designed and synthesized a dual-gated nanodrug based on MXene, which can not only specifically target pancreatic cancer cells and induce ICD, but also effectively regulate the immune microenvironment. Tumor cells undergo ferroptosis, a typical kind of ICD, which allowed a large number of tumor-associated antigens (TAA) to be released from the cytoplasm into the microenvironment. Dendritic cells (DCs) were attracted and promoted maturation. Activated DCs processed and presented TAA to T cells, which was a necessary process for T cell activation and ultimately heated up the cold tumor immune microenvironment of pancreatic cancer. In general, our work is an interesting and important exploration, aiming to apply MXene nanoparticles with great potential to the treatment of pancreatic cancer, and provide new ideas and directions for the biomedical application of related materials.