Amorphous CaCO3-bioreactor for tumor microenvironment regulation to reinforce tumor chemoimmunotherapy

Developing efficient nanomedicines to modulate the immunosuppressive tumor microenvironment (TME) is a highly sought-after method for improving the adverse clinical outcomes of immunotherapy. In this study, we designed a novel tumor immune stimulatory nanomedicine to regulate the immunosuppressive TME in multiple directions. This nanomedicine is liposome-modified amorphous calcium carbonate (ACC) nanoparticles (referred to as CEL/ACC-LP NPs) loaded with chemotherapeutic medication celastrol (CEL). CEL/ACC-LP NPs explosively release calcium ions (Ca 2+ ) and CEL in the tumor acidic microenvironment, and rapidly deplete H + to alleviate the tumor acidic microenvironment, exhibiting intrinsic immune regulatory activity in synergistic tumor chemoimmunotherapy. CEL induces reactive oxygen species (ROS) to promote Ca 2+ influx, exacerbating cellular Ca 2+ overload. In addition, CEL/ACC-LP NPs can cause unique immunogenic cell death (ICD) effects. Therefore, the multi-directional regulation of tumor cells through simple nano preparation will offer a potent approach to improve the efficacy of chemoimmunotherapy.