A multifunctional CaCO bioreactor coated with coordination polymers enhances cancer immunotherapy.

Designing effective nanomedicines to induce durable anti-tumor immunity represents a promising strategy for improving moderate immune stimulation. In this study, we engineered a multifunctional nanoreactor (named SCGFP NPs) for remodeling the tumor microenvironment (TME) to improve the therapeutic efficacy of immunotherapy. The core of SCGFP NPs consists of CaCO loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca and SN38. The SN38-induced intracellular Ca accumulation and exogenous Ca synergistically trigger immunogenic cell death (ICD) through sustained Ca overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe induces tumor cell necrosis, further enhancing ICD activation. Additionally, SN38 upregulates PD-L1, amplifying tumor responsiveness to immune checkpoint inhibitors (ICIs). This study indicates that SCGFP NPs, through the integration of a trimodal therapeutic strategy, hold enormous potential for various types of tumor immunotherapy through distinct mechanisms or synergistic effects.