Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 58, Issue 36, Pages 12680-12687Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201906288
Keywords
cancer therapy; immunotherapy; organic nanoparticles; photoactivation; prodrugs
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Funding
- Nanyang Technological University [M4081627]
- Singapore Ministry of Education [RG133/15 M4011559, MOE2016-T2-1-098]
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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 (O-1(2)) cleavable linkers. Upon NIR laser irradiation, OSPS generates both heat and O-1(2) to exert combinational phototherapy not only to ablate tumors but also to produce tumor-associated antigens. More importantly, NIR irradiation triggers the cleavage of O-1(2)-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.
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