Sonogenetic nanosystem activated mechanosensitive ion channel to induce cell apoptosis for cancer immunotherapy

Currently, tumor immunotherapy based on small chemical molecules has become a promising antitumour therapeutic strategy. However, its clinical application has been mainly limited by the damage to normal tissues caused strong side effects. Here we show that a sonogenetic nanosystem to activate mechanosensitive ion channels to induce cell apoptosis for achieving accurate adjustable and safe cancer immunotherapy. This system consisted of nanogel, MSCL (mechanosensor) plasmids and transfection reagent PEI. Nanogel was used as a carrier to realize MSCL plasmids and PEI delivery into tumor cells. Mechanosensitive MSCL ion channels express in cells surfaces responding to ultrasound signaling. Upon ultrasound, MSCL ion channels open to cause continuous Ca2+ overload activating cell apoptosis, so as to accurately regulate cell apoptosis without affecting other tissues cells. In vivo, the melanoma model of C57BL-6 mice was studied as an example. The results show that cell fragments produced by cell apoptosis act as tumor-associated antigens to safely promote DC maturation and CD8+T cell activation up to 17.7% and 17.6%, respectively. Together, this sonogenetic nanosystem may provide a new method for cancer immunotherapy and also expand the application of sonogenetics.