Polydopamine-armed microalgal oxygenerator targeting the hypoxia-adenosine axis to boost cancer photothermal immunotherapy

Hypoxia induces the generation of immunosuppressive adenosine within the tumor microenvironment (TME) and further impedes the activation of antitumor immunity triggered by photothermal therapy (PTT). In this study, a photothermal microalgae system (PTA) based on Chlorella sorokiniana (C. soro) is developed to boost antitumor immune responses by targeting the hypoxia-adenosine axis. PTA is constructed by coating polydopamine (PDA), a promising photothermal agent with good biocompatibility, on the surface of C. soro. Due to the inherent photosynthetic capability of microalgae, PTA in situ generates O2 within the tumor under irradiation at 660 nm for hypoxia alleviation, thereby downregulating the level of adenosine to reverse the immunosuppression in TME. Subsequently, this reshaped TME promotes the activation of antitumor immunity induced by PTT, which is realized by the coated PDA layer on C. soro under irradiation at 808 nm. In a mouse model of 4T1 tumors, PTA significantly weakens the immunosuppression in the TME, elicits robust antitumor immune responses, and suppresses tumor growth. Together, this strategy highlights the potential of leveraging living photosynthetic microalgae as an oxygenerator to boost cancer photothermal immunotherapy.