Biomimetic Manganese Mineralized Chemoimmunological Microneedles Priming cGAS-STING for Robust Cascade Cancer Therapy

Dissolvable microneedle-based transdermal superficial technique demonstrates promised integrative potential for triple-negative breast cancer (TNBC) therapy, yet their insufficient mechanical strength restricts to puncture, attributed to the high-density tumor stroma and elasticity of TNBC, limiting long-distance therapeutics penetration and profound treatment in situ, posing a significant barrier to achieving effective therapy for TNBC management. Inspired by biomineralization, herein, a novel strategy is presented for a robust microneedle involving manganese phosphate biomimetic mineralization, which is characterized by a homogeneous inorganic-organic intercross modification, achieving high mechanical strength and solubility. Furthermore, the chemotherapy drug, doxorubicin (DOX), can be facilely integrated into this biomimetic process, facilitating chemoimmunological microneedles (MD-MN). Subsequently, the MD-MN provides high robustness for tumor injection followed by releasing manganese and DOX within the tumor, and the manganese can reduce tumor stroma and enhance deep DOX infiltration, exerting significant cancer cell apoptosis. Furthermore, manganese elements can reverse the immunosuppressive microenvironment by activating cGAS-STING, which taken together, constructs a boosted cascade chemoimmunological therapy for TNBC. These achievements present a successful integrative strategy for circulated cascade chemoimmunological treatment for TNBC, indicating a great potential of biomineralization-based cancer medicine, further demonstrating insights into biomimetic physiological reactions for material construction and translational medicine.