Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

Abstract Background Despite the synergy of immune checkpoint blockade (ICB) therapy and photodynamic therapy (PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains great challenge. Methods Programmed death-ligand 1 antibody (αPD-L1) and photosensitizer chlorin e6 (Ce6) were loaded in polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel for flexible local photoimmunotherapy with merely single-dosed administration. Phototriggered drug release and ROS generation of Lp(DHA)@CP Gel were evaluated in vitro . To investigate tumor therapeutic effect, NIR laser of 671 nm was used to irradiate tumor site after a single dose of peritumoral administration of Lp(DHA)@CP Gel of 4T1-bearing mice. Results With syringe-injectable and self-healing property, Lp(DHA)@CP Gel showed a photo-triggered release of αPD-L1 repeatedly induced to in situ in response to PDT for at least 11 days. Additionally, Lp(DHA)@CP Gel exhibited prominent antitumor efficacy both in vitro and in vivo . The on-demand treatment can maximize the patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. Furthermore, the immunogenic cell death (ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade released αPD-L1 to synergistically boost the immunotherapy. Conclusion Lp(DHA)@CP Gel is a flexible medication platform, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.