Sono-Immunotherapy for Lung Cancer Utilizing Targeted Preactivated Neutrophil Membrane-Coated Nanoparticles

Although targeted therapy and immunotherapy have shown encouraging clinical results in treating lung cancer, they can only benefit a handful of patients. Therefore, there is an urgent need to develop novel anticancer strategies to treat lung cancer. Here, we report a cancer-targeting strategy for the treatment of lung cancer via coating pretreated neutrophil membranes (pM) stimulated with lung cancer cells onto hollow manganese dioxide (HMnO₂) cores, and further development of sono-immunotherapeutic nanoparticles (MTpMAb@R) by decoration of sonosensitizers and anti-CTLA-4 antibodies on the HMnO₂ nanoshells for activatable tumor sono-immunotherapy. The pM-coated nanoparticles with high expression of chemokine receptors target tumors more efficiently. With ultrasound irradiation, MTpMAb@R nanoparticles can both generate immunogenic cell death through the sonodynamic effect and block the immune checkpoint by releasing anti-CTLA-4 antibodies, which concurrently induces a sequence of antitumor immune responses. As a result, such a synergistic therapeutic action is achieved by combined sono-immunotherapy. Therefore, this study represents a promising strategy for treating lung cancer with high precision.