Photodynamic therapy (
PDT) has shown the potential of triggering systemic antitumor immune responses. However, while the
oxygen-deficient hypoxic tumor microenvironment is
a factor that limits the
PDT efficacy, the immune responses after conventional
PDT usually are not strong enough to eliminate metastatic
tumors. Herein, a light-triggered in situ gelation system containing
photosensitizer-modified
catalase together with poly(
ethylene glycol) double
acrylate (PEGDA) as the polymeric matrix is designed. Immune adjuvant nanoparticles are further introduced into this system to trigger robust antitumor immune responses after
PDT. Following local injection of the mixed precursor
solution into
tumors and the subsequent light exposure, polymerization of PEGDA can be initiated to induce in situ gelation. Such hybrid
hydrogel with long-term
tumor retention of various agents and the ability to enable persistent tumor hypoxia relief can enable multiple rounds of
PDT, which results in significantly enhanced immune responses by multiround stimulation. Further combination of such gel-based multiround
PDT with anticytotoxic T-lymphocyte antigen-4 checkpoint blockade offers not only the abscopal effect to inhibit growth of distant
tumors but also effective long-term immune memory protection from rechallenged
tumors. Therefore, such a light-triggered in situ gelation system by a single-dose injection can enable greatly enhanced photoimmunotherapy by means of repeated stimulations.