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.
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