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

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 enhance their cytotoxicity and tolerance, improving the living activity in the tumor area. The innate chlorophyll and unique optical property make Algae@SiO₂ possess dual imaging ability, namely, photoacoustic imaging and fluorescence imaging. Algae@SiO₂ accumulated in tumor sites could generate oxygen in situ by external light-mediated photosynthesis, relieve tumor hypoxia, and then enhance the efficiency of radiation therapy. As a natural photosensitizer, the released chlorophyll from Algae@SiO₂ could provide reactive oxygen species to kill the cancer cells for the cascaded photodynamic therapy. The significant suppression of tumor growth in the mice bearing 4T1 tumor successfully demonstrates 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.