Biomineralized Biohybrid-Algae for Tumor Hypoxia Modulation and Cascade Radio-Photodynamic Therapy

The biomineralization of biomaterials has shown extraordinary potential in cancer treatment, but the exploration of their in vivo applications is still insufficient. Here, we report a biohybrid microalgae system using a biomineralization approach to improve their biocompatibility, while keeping their living activities for radiation and photodynamic synergistic therapy in breast cancer. The biohybrid-algae (Algae@SiO2) synthesized by a one-step biomimetic silicification method could significantly enhanced their cytotoxicity and tolerance, improve the living activity in the tumor area. The innate of chlorophyll and unique optical property make the Algae@SiO2 possess dual imaging ability, including photoacoustic imaging (PAI) and fluorescence imaging (FI). Algae@SiO2 accumulated in tumor sites could generate oxygen in situ by the external light-mediated photosynthesis, relieve the tumor hypoxia, then enhance the efficiency of radiation therapy. As a natural photosensitizer, the released chlorophyll from Algae@SiO2 could provide reactive oxygen species (ROS) to generate cancer cell apoptosis for the cascaded photodynamic therapy. The significant suppression of tumor growth and metastasis in the 4T1 breast tumor-bearing mice successfully demonstrate the promising anti-tumor effect of the Algae@SiO2 mediated synergistic therapy. Our results show that biohybrid-algae, integrated with PAI/FI dual imaging, radiosensitization and cascaded photothermal therapy, is a promising multifunctional efficient biosystem for cancer treatment.