A phenolic based tumor-permeated nano-framework for immunogenic cell death induction combined with PD-L1 immune checkpoint blockade

Abstract

A critical obstacle for programmed death ligand 1 (PD-L1) immune checkpoint blockade immunotherapy is the insufficient T cell infiltration and low immunogenicity of tumor cells. Improving tumor immunogenicity through immunogenic cell death (ICD) can make tumor sensitive to PD-L1 checkpoint blockade immunotherapy. Herein, a phenolic based tumor-permeated nano-framework (EGPt-NF) was fabricated by cross-linking phenylboric acid modified platinum nanoparticles (PBA-Pt, ICD inducer) and epigallocatechin-3-O-gallate (EGCG, PD-L1 inhibitor) via pH-reversible borate ester. In particular, PBA-Pt could not only induce ICD cascade but also relieve tumor hypoxia. Consequently, EGPt-NF could effectively promote dendritic cell maturation and downregulate PD-L1 expression in tumor cells. Furthermore, EGPt-NF could also relieve tumor hypoxia to facilitate cytotoxic T lymphocyte infiltration and IFN-γ secretion. The synergistic effect of EGPt-NF could effectively improve tumor immunogenicity and amplify the therapeutic outcomes of cancer immunotherapy, resulting in a strong antitumor immune response in primary tumor and metastasis inhibition. Our simple approach expands the application of platinum-based drug delivery systems for cancer immunotherapy.