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

Despite the synergy of immune checkpoint blockade (ICB) therapy and photodynamic (PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a challenge. Here, we present polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6 (Ce6) programmed death-ligand 1 antibody (αPD-L1) for local photoimmunotherapy merely single-dosed administration. The presence acid (docosahexaenoic acid, DHA) doped particle membrane endows liposomes flexibly reactive oxygen species (ROS)-responsive release capability, which was attributed to abundant unsaturated groups. αPD-L1 repeatedly induced situ response PDT under photo-exposure. immunogenic cell death (ICD) effect evoked tumor “hot” one, then assisted cascade released synergistically boost immunotherapy. After single dose peritumoral administration Gel, on-demand treatment can maximize patient compliance safety by adjusting behaviors via photo on-off switch. This work presents medication platform, showing improving objective rate ICB minimizing its systemic toxicity.