Abstract
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 a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6 (Ce6) and programmed death-ligand 1 antibody (αPD-L1) for flexible local photoimmunotherapy with merely single-dosed administration. The presence of polyunsaturated fatty acid (docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species (ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. 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. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.
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