Chimeric Peptide Functionalized Immunostimulant to Orchestrate Photodynamic Immunotherapeutic Effect by PD-L1 Deglycosylation and CD47 Inhibition.

Breast cancer utilizes diverse immunosuppressive mechanisms to evade immune surveillance, thereby impairing immunotherapeutic effects. In this work, a chimeric peptide functionalized immunostimulant (designated as aGlyR) is fabricated to boost photodynamic immunotherapy through PD-L1 deglycosylation and CD47 inhibition. The photosensitizer protoporphyrin IX (PpIX) is conjugated to a PD-L1 deglycosylation peptide via a hydrophilic PEG linker, yielding the chimeric peptide Fmoc-K(PpIX)-PEG-GFTATPPAPDSPQEP.

Chimeric Peptide-Engineered Polyprodrug Enhances Cytotoxic T Cell Response by Inducing Immunogenic Cell Death and Upregulating Major Histocompatibility Complex Class I.

Tumor-specific cytotoxic T cell immunity is critically dependent on effective antigen presentation and sustained signal transduction. However, this immune response is frequently compromised by the inherently low immunogenicity of breast cancer and the deficiency in major histocompatibility complex class I (MHC-I) expression. Herein, a chimeric peptide-engineered stoichiometric polyprodrug (PDPP) is fabricated to potentiate the cytotoxic T cell response, characterized by a high drug loading capacity and precise stoichiometric drug ratio, of which the immunogenic cell death (ICD) inducer of protoporphyrin IX (PpIX) and the epigenetic drug of decitabine (DAC) are condensed into a polyprodrug called PpIX-DAC.