Organic Semiconducting Pro-nanostimulants for Near-Infrared Photoactivatable Cancer Immunotherapy

In this study, an organic semiconducting pro-nanostimulant (OSPS) with a near-infrared (NIR) photoactivatable immunotherapeutic action for synergetic cancer therapy is presented. OSPS comprises a semiconducting polymer nanoparticle (SPN) core and an immunostimulant conjugated through a singlet oxygen (¹O₂) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and ¹O₂ to exert combinational phototherapy not only to ablate tumors but also to produce tumor-associated antigens. More importantly, NIR irradiation triggers the cleavage of ¹O₂-cleavable linkers, triggering the remote release of the immunostimulants from OSPS to modulate the immunosuppressive tumor microenvironment. Thus, the released tumor-associated antigens in conjunction with activated immunostimulants induce a synergistic antitumor immune response after OSPS-mediated phototherapy, resulting in the inhibited growth of both primary/distant tumors and lung metastasis in a mouse xenograft model, which is not observed for sole phototherapy.