A multifunctional CaCO3 bioreactor coated with coordination polymers enhances cancer immunotherapy

Abstract

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 CaCO₃ loaded with SN38, prepared by the gas diffusion method, and coated with a significant amount of gallic acid-Fe³⁺-PEG coordination polymer on the surface. In the acidic TME, SCGFP NPs explosively release exogenous Ca²⁺ and SN38. The SN38-induced intracellular Ca²⁺ accumulation and exogenous Ca²⁺ synergistically trigger immunogenic cell death (ICD) through sustained Ca²⁺ overload. The ablation of tumors with high-intensity photothermal therapy (PTT) by near-infrared (NIR) irradiation of GA-Fe³⁺ 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.

Keywords: Ca(2+) overload; Cancer immunotherapy; Chemotherapy; Immunogenic cell death; Photodynamic therapy.