Biomineralization-inspired nanosheet transformation potentiates cancer therapy through precise embolization and antitumor immunity restoration

Tumor vasculature targeting therapy represents a promising approach to inhibit tumor growth by disrupting the supply of nutrients and oxygen. However, achieving tumor-specific embolization remains a great challenge while the severe disruption of the vascular supply is supposed to aggravate tumor immunosuppression. Inspired by natural biomineralization process of magnesium phosphate, we developed a novel approach combining Mg(OH)₂ nanosheets with microneedles (MNs) for precise tumor embolization and enhanced immunotherapy. Triggered by elevated concentrations of hydrogen ions and phosphate in the tumor microenvironment (TME), Mg(OH)₂ nanosheets undergo a transformation into biomineralized magnesium phosphate precipitates for tumor-specific embolization. Furthermore, these nanosheets exhibit intrinsic immunomodulatory properties, capable of reversing immunosuppression by neutralizing the acidic TME. Additionally, they induce dendritic cell maturation and oxidative stress in tumor cells, triggering immunogenic cell death and eliciting robust antitumor immune responses. To further enhance the efficiency, the MN platform enables co-delivery of the antiangiogenic drug sunitinib with Mg(OH)₂ nanosheets. The satisfactory antitumor effects of the Mg(OH)₂-MNs platform in vivo were validated in a 4T1 tumor-bearing mice model. Transcriptomics analysis confirmed the activation of strong antitumor immunity and successful immunosuppression reversal. This study proposes a promising biomineralization-inspired strategy to construct immunomodulatory nanomaterials for tumor-specific embolization and enhanced immunotherapy.