Microwave
thermotherapy (MT) is a clinical local tumor ablation
modality, but its applications are limited by its therapeutic efficacy
and safety. Therefore, developing sensitizers to optimize the outcomes
of MT is in demand in clinical practice. Herein, we engineered a special
nanoframework (i.e., FdMI) based on a fucoidan-decorated zirconium
metal–organic framework incorporating manganese ions and liquid
physisorption for microwave tumor ablation. The monodisperse nanoframework
exhibited both microwave thermal effects and microwave dynamic effects,
which could effectively kill cancer cells by efficient intracellular
drug delivery. Through fucoidan-mediated targeting of P-selectin in
the tumor microenvironment (TME), the FdMI effectively accumulated
in tumor regions, leading to significant eradication of orthotropic
triple-negative breast cancer (TNBC) and aggressive Hepa1–6
liver tumors by the synergistic effects of microwave thermotherapy/dynamic
therapy (MT/MDT). The eradication of primary tumors could activate
systemic immune responses, which effectively inhibited distant TNBC
tumors and lung metastasis of Hepa1–6 liver tumors, respectively.
This work not only engineered nanoparticle sensitizers for tumor-targeted
synergistic MT/MDT but also demonstrated that nanocarrier-based microwave
tumor ablation could stimulate antitumor immunity to effectively inhibit
distant and metastatic tumors, demonstrating the high potential for
effectively managing advanced malignant tumors.