Metal ions and nanometallic materials in antitumor immunity: Function, application, and perspective

Abstract

The slightest change in the extra/intracellular concentration of metal ions results in amplified effects by signaling cascades that regulate both cell fate within the tumor microenvironment and immune status, which influences the network of antitumor immunity through various pathways. Based on the fact that metal ions influence the fate of cancer cells and participate in both innate and adaptive immunity, they are widely applied in antitumor therapy as immune modulators. Moreover, nanomedicine possesses the advantage of precise delivery and responsive release, which can perfectly remedy the drawbacks of metal ions, such as low target selectivity and systematic toxicity, thus providing an ideal platform for metal ion application in cancer treatment. Emerging evidence has shown that immunotherapy applied with nanometallic materials may significantly enhance therapeutic efficacy. Here, we focus on the physiopathology of metal ions in tumorigenesis and discuss several breakthroughs regarding the use of nanometallic materials in antitumor immunotherapeutics. These findings demonstrate the prominence of metal ion-based nanomedicine in cancer therapy and prophylaxis, providing many new ideas for basic immunity research and clinical application. Consequently, we provide innovative insights into the comprehensive understanding of the application of metal ions combined with nanomedicine in cancer immunotherapy in the past few years. Graphical Abstract

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Copper chelating structures have cuprous Cu1+ (copper (I)) and cupric Cu2+ (copper (II)) that mainly bond with C, N, O, or S donor atoms [103][104]. This is because of the Jan-Teller effect in their d-orbitals, copper ions exist in two coordination redox states [22]. Their ligands are cysteine and methionine for S donor atoms [105] and histidine, glutamic acid, and aspartic acid for N or O donor atoms [106].…”

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

“…Copper chelating structures have cuprous Cu 1+ (copper(I)) and cupric Cu 2+ (copper(II)) that mainly bond with C, N, O, or S donor atoms [ 98 , 99 ]. This is because of the Jahn–Teller effect in their d-orbitals; copper ions exist in two coordination redox states [ 22 ]. Their ligands are cysteine and methionine for S donor atoms [ 100 ] and histidine, glutamic acid, and aspartic acid for N or O donor atoms [ 101 ].…”

“…This will alter MBD’s perspectives and generate new drug discovery insight maps [ 21 ]. In modern medicine, the understanding of metal-ion functions [ 22 ] and diagnosis at the molecular level [ 23 ] have become inevitable consequences of delivering new MBD in medicinal bioinorganic chemistry [ 24 , 25 ]. There is still inadequate effort devoted at mechanistic levels [ 26 ] towards providing an alternative, targeted, and rational approach [ 27 ] to supplement screening of novel chemical entities for biological activity [ 21 ].…”

Copper-induced injectable hydrogel with nitric oxide for enhanced immunotherapy by amplifying immunogenic cell death and regulating cancer associated fibroblasts

“…1 . Compared with traditional hydrogels, due to the photothermal conversion performance of Cu, the hydrogel showed hyperthermia as PTT to eradicate cancer cells for local cancer treatment with NIR laser irradiation [ 40 ]. In addition, the Cu 2+ from injectable hydrogel can be reduced to Cu + by high expression of glutathione (GSH) under the action of tumor acidic environment, which further reacted with hydrogen peroxide (H 2 O 2 ) to produce cytotoxic hydroxyl radical (·OH) for depletion of cancer cells [ 41 ].…”