Abstract
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 (Ca2+) 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 Ca2+ influx, exacerbating cellular Ca2+ 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.
Published Version
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