Supramolecular Antigen Peptide Nanoparticles for Enhanced Photodynamic Therapy and Immunotherapy against Tumors

Abstract

Antigen peptide-based immunotherapy holds significant promise for tumor treatment by eliciting targeted immune responses against tumor cells. However, current methods often face limitations in achieving effective antigen delivery and immune activation. Addressing these challenges through novel delivery systems and immunomodulatory strategies is crucial for improving the clinical efficacy of this therapy. Herein, a supramolecular system based on the self-assembly of the human papillomavirus (HPV) E7 antigen peptide is established by utilizing a Schiff base-mediated self-assembly approach. The E7 antigen peptide nanoparticles (E7 NPs) are further functionalized by loading chlorin e6 (Ce6) and decorating with bovine serum albumin (BSA), generating BSA/E7/Ce6 NPs. The BSA/E7/Ce6 NPs exhibited remarkable photodynamic effects in the inhibition of tumor cells and significantly improved tumor accumulation. Especially, the BSA/E7/Ce6 NPs improved antitumor immune responses of the E7 antigen by effectively activating cytotoxic T lymphocytes. The combination therapy integrating BSA/E7/Ce6 NPs with photodynamic therapy demonstrated a 1.8-fold increase in CD3⁺CD8⁺ T cells compared to monotherapy groups, leading to significantly enhanced antitumor effects. Our findings demonstrate that supramolecular antigen peptide nanomaterials can be established as drug delivery systems while retaining their original antigenicity, providing a versatile strategy for realizing enhanced antitumor immunotherapy.