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

Area of Science:

• Biomedical Engineering
• Immunotherapy
• Nanotechnology

Background:

• Peptide therapeutics for cancer immunotherapy face challenges with bioavailability, clearance, and tumor targeting.
• Effective delivery systems are crucial for enhancing the efficacy of immunotherapeutic peptides.

Purpose of the Study:

• To develop a biomimetic, photothermal-responsive liposomal system for enhanced peptide delivery in tumor immunotherapy.
• To combine peptide immunotherapy with photothermal therapy for synergistic anti-tumor effects.

Main Methods:

• Fabrication of thermosensitive liposomes (1,2-dipalmitoyl-sn-glycero-3-phosphocholine) loaded with indocyanine green (ICG) for photothermal release.
• Surface coating of liposomes with platelet membranes to improve tumor targeting and circulation time.
• Fluorination of peptides to enhance stability and disruption of PD-L1 post-translational modifications.

Main Results:

• The liposomal system demonstrated controlled peptide release upon photothermal stimulation.
• Photothermal stimulation induced immunogenic cell death (ICD), enhancing the anti-tumor immune response.
• In vivo studies showed significant suppression of tumor growth in solid and diffuse tumors, alongside the induction of immune memory.

Conclusions:

• The developed bioengineering platform effectively integrates peptide delivery with photothermal therapy for advanced tumor immunotherapy.
• This novel approach offers a promising strategy for overcoming limitations in current peptide-based cancer treatments.
• The system enhances anti-tumor immunity through improved peptide stability, targeted delivery, and synergistic therapeutic effects.