Copper‐Based Nanoscale Coordination Polymers Augmented Tumor Radioimmunotherapy for Immunogenic Cell Death Induction and T‐Cell Infiltration

Abstract

Insufficient T‐cell infiltration seriously hinders the efficacy of tumor immunotherapy. Induction of immunogenic cell death (ICD) is a potentially feasible approach to increase T‐cell infiltration. Since ionizing radiation can only induce low‐level ICD, this study constructs Cu‐based nanoscale coordination polymers (Cu‐NCPs) with mixed‐valence (Cu+/Cu2+), which can simultaneously and independently induce the generation of Cu+‐triggered hydroxyl radicals and Cu2+‐triggered GSH elimination, to synergize with radiation therapy for potent ICD induction. Markedly, this synergetic therapy remarkably enhances dendritic cell maturation and promotes antitumor CD8+ T‐cell infiltration, thereby potentiating the development of checkpoint blockade immunotherapies against primary and metastatic tumors.

Comprehensive multiomics analysis of cuproptosis-related gene characteristics in hepatocellular carcinoma

“…A recent study revealed that magnesium can promote CD8 T cell activation and high expression levels of PD-1 by regulating metabolic reprogramming to enhance the efficacy of immunotherapy ( Lötscher et al, 2022 ). In addition, some studies have shown that copper is related to T cell infiltration and recruitment ( Kaddatz et al, 2021 ; Wang et al, 2021 ). However, whether these cuproptosis-related genes can affect the immune characteristics of HCC remains largely unknown.…”

Immunogenic Cell Death Activates the Tumor Immune Microenvironment to Boost the Immunotherapy Efficiency

“…[180] This Cu + /Cu 2+ -based RT noticeably intensified the ICD effect, increased the population of matured DCs from 19.7% to 35.1% in lymph nodes (Figure 12e). Combined with anti-PD-L1 antibodies, the Cu-based nanostructure effectively inhibited the growth of distant tumors (Figure 12f) and promoted [180] Copyright 2021, Wiley-VCH.…”

“…CuSO 4 and 5′‐guanosine monophosphate (5′‐GMP) self‐assembled to prepare a mixed valence Cu + /Cu 2+ ‐based nanoscale coordination polymer ( Figure 12 a ), in which Cu + could decompose H 2 O 2 to •OH and Cu 2+ deplete GSH to GSSG (Figure 12b–d ). [ 180 ] This Cu + /Cu 2+ ‐based RT noticeably intensified the ICD effect, increased the population of matured DCs from 19.7% to 35.1% in lymph nodes (Figure 12e ). Combined with anti‐PD‐L1 antibodies, the Cu‐based nanostructure effectively inhibited the growth of distant tumors (Figure 12f ) and promoted intratumoral CD8 + T cells infiltration and IFN‐ γ secretion for potent immune responses (Figure 12g,h ).…”

Mixed‐Metal MOF‐Derived Hollow Porous Nanocomposite for Trimodality Imaging Guided Reactive Oxygen Species‐Augmented Synergistic Therapy

“…Encouragingly, the coordination of Cu 2+ ions with organics is a feasible strategy to obtain Cu + ions. [ 22 ] Thus, we introduce Cu 2+ ions, in the precursors of ZIF‐90, Zn 2+ ions, and imidazol‐2‐carboxyaldehyde (2‐ICA), to prepare mixed‐metal Cu/Zn‐MOF at room temperature. Transmission electron microscopy (TEM) images of the Cu/Zn‐MOFs with different Cu contents demonstrated their sphere morphology with the size of ≈110, 210, and 120 nm derived from ZIF‐90 ( Figure a).…”