The Immunomodulatory Potential of Copper and Silver Based Self-Assembled Metal Organic Biohybrids Nanomaterials in Cancer Theranostics

Abstract

Copper high aspect ratio structures (CuHARS) and silver cystine nanoparticles (AgCysNPs) are two unique micro/nano particles under study here that show extensive anti-cancer effects on a glioma tumor cell line. These micro/nano particles have shown potent toxicity in the presence of inflammatory stimulus (combination of tumor necrosis factor, [TNF] and lipo-polysaccharide, LPS). CuHARS with a concentration of 20 μg/ml uniquely increased the catalytic generation of nitric oxide (NO), an important contributor in the immune system. This NO was generated in a cell culture tumor microenvironment (TME) in the presence of 25 µM S-nitrosothiol (cysteine-NO) and the inflammatory stimulus. CuHARS increased the NO production by 68.75% when compared to untreated glioma cells with CysNO and inflammatory stimulus. The production of NO was significantly higher under similar circumstances in the case of normal primary structural cells like brain microvascular endothelial cells (BMVECs). The production of NO by BMVECs went up by 181.25% compared to glioma cells. This significant increase in the NO concentration could have added up to tumorigenesis but the anti-cancer effect of CuHARS was prominent enough to lower down the viability of glioma cells by approximately 20% and increased the metabolism of structural cells, BMVECs by approximately 200%. The immunomodulatory effect of NO in the TME under these circumstances in the presence of the novel micro/nano material, CuHARS has risen up compared to the effect of inflammatory stimulus alone. The potency and specific nature of these materials toward tumor cells may make them suitable candidates for cancer treatment. Successive treatment of CuHARS to glioma cells also proved to be an effective approach considering the decrease in the total count of cells by 11.84 fold in case of three successive treatments compared to a single dose which only decreased the cell count by 2.45 fold showing the dose-dependent increasing toxicity toward glioma cells. AgCysNPs are another potent nanomaterial which also proved its significant toxic nature toward tumor cell lines as demonstrated here, but their immunomodulatory response is still unclear and needs to be explored further.

Cuproptosis scoring system to predict the clinical outcome and immune response in bladder cancer

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Prognostic analysis of cuproptosis-related ferroptosis genes in lung adenocarcinoma

“…Moreover, mounting evidence suggests that dysregulation of copper homeostasis can in uence tumor cell growth and cause tumor cell death [19]. And copper plays critical roles in tumor immunology and anti-cancer treatment [20,21]. Mechanistically, Tsvetkov et al demonstrated that excessive intracellular copper mediates cell death under the guidance of mitochondrial iron-sulfur protein (Fe-S) FDX1.…”

Advances in Copper-Based Biomaterials With Antibacterial and Osteogenic Properties for Bone Tissue Engineering

“…At the same time, biocompatibility and antibacterial ability must also be achieved. At present, most experiments evaluate the toxicity of copper-based biomaterials by testing them with bone marrow stem cells, osteoblasts, and other cells, and using in vivo experiments in small animals ( Prajapati et al, 2020 ). However, these do not simulate the human body’s true response to toxicity, so more clinical trial results are needed.…”