Biodegradable Ca²⁺ Doped Mesoporous Silica Nanoparticles Promote Chemotherapy Synergism with Calcicoptosis and Activate Anti-Tumor Immunity

Mesoporous silica nanoparticles (MSNs), an excellent carrier material, have been widely used in tumor therapy as a vector for numerous therapeutic substances to boost therapeutical efficiency and specificity, such as loading them with chemotherapy drugs to improve the efficacy of chemotherapy. Nevertheless, they still face hurdles, such as lack of specificity and poor efficacy of monotherapy. The construction of multifunctional MSNs with excellent therapeutic effects by introducing metal ions has attracted the attention of many researchers. Herein, we demonstrated a calcium doped, chemotherapy drug doxorubicin (Dox) loaded, specific degradation nanoplatform, prepared using the sol–gel method by introducing calcium ions into an MSN framework, which enabled the doped nanoplatform to enhance chemotherapy and activate anti-tumor immune response. As a proof of concept, the doping of Ca²⁺ endowed MSNs with excellent specific degradation and pH responsive drug release, and enabled the synergy of chemotherapy and calcicoptosis. Furthermore, this nanoplatform also effectively elicited immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs), realizing the activation of the anti-tumor immune system. The Ca²⁺ doped MSNs (CMSNs), that can activate immune response with specific degradation capability, demonstrate a practical strategy for the effective synergy between chemotherapy and calcicoptosis, providing a new paradigm for promoting chemotherapy-related treatment.