PD-L1-Targeting Biomimetic Photoresponsive Thermosensitive Liposomes for Triple-Negative Breast Cancer

Peptide-based therapeutic strategies offer considerable potential for tumor immunotherapy but suffer from poor systemic bioavailability, rapid plasma clearance, and limited tumor-targeting efficiency. To address these challenges, a biomimetic, photothermal-responsive liposomal delivery system was developed that enables precise delivery of immunotherapeutic peptides while enhancing the synergistic effects of photothermal therapy. This system enhances peptide stability through fluorination, disrupts post-translational modifications of PD-L1, and promotes its degradation, thereby amplifying the anti-tumor immune response. The carrier core consisted of thermosensitive 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes loaded with the low-toxicity photosensitizer indocyanine green (ICG), which facilitated controlled peptide release via the photothermal effect. Simultaneously, mild photothermal stimulation induced immunogenic cell death (ICD), further strengthening anti-tumor immunity. To enhance tumor targeting, extend systemic circulation time, and improve drug accumulation at tumor sites, the carrier surface was coated with a platelet membrane, which increased biocompatibility and promoted immune evasion. Notably, in vivo studies demonstrated that the developed bioengineering platform significantly suppressed tumor growth in both solid and diffuse malignant tumors while inducing persistent immune memory, thereby facilitating long-term anti-tumor immune responses. Collectively, this approach establishes a novel framework for integrating peptide drug delivery with photothermal therapy, offering a promising strategy for advancing tumor immunotherapy.