Engineered microalgae for photo-sonodynamic synergistic therapy in breast cancer treatment

Dynamic therapies such as photodynamic therapy (PDT) and sonodynamic therapy (SDT) have potential in cancer treatment. Microalgae have attracted increasing attention because of their high active mobility, flexibility in terms of functionality, and good biocompatibility. In this study, surface-engineered microalgae Chlorella vulgaris (Chl) modified with metal‒organic framework (MOF) nanoparticles (denoted Chl-MOF) are successfully developed for synergistic photo-sonodynamic therapy and immunotherapy. The resulting Chl-MOF can be used as an oxygenator for O₂ generation through Chl-mediated photosynthesis, alleviating tumor hypoxia. Furthermore, Chl-MOF produces reactive oxygen species (ROS) during laser and ultrasound (US) irradiation, further augmenting the photo-sonodynamic effects and enhancing tumor cell apoptosis. Owing to the high mobility of Chl, cellular uptake efficiency and accumulation in deep tumor sites are 5.2-fold and 3.3-fold higher, respectively, for Chl-MOF than for the MOF. Owing to the immunomodulatory effects of Chl, Chl-MOF can increase natural killer (NK) cell cytotoxic activity, increase dendritic cell (DC) antigen-presenting ability, reverse the establishment of an immunosuppressive tumor microenvironment (TME), and induce a relatively strong antitumor immune response. Chl-MOF can effectively reduce breast cancer size by 88.8 % in vitro and in vivo via synergistic photo-sonodynamic therapy and immunotherapy. These intriguing properties of the combination of Chl and MOF provide promising platform for cancer theranostic applications. STATEMENT OF SIGNIFICANCE: : • Chl acts as an O₂ generator for alleviating hypoxia in tumors. • The high mobility of Chl resulted in 3.3-folds higher tumor accumulation. • The Chl-MOF can induce synergistic photo-sonodynamic effects and a relatively strong antitumor immune response. • Chl-MOF effectively reduce breast cancer size by 88.8 % via synergistic therapies.