Anti-inflammatory efficacy of SMP24-conjugated ZnOCuO and AgCuO nanocarriers in Ehrlich carcinoma-bearing: histological and molecular evidence through EGFR/P38 pathway and cytokine modulation

Abstract

Background and aim Chronic inflammation plays a critical role in tumor progression through dysregulated cytokine networks and key signaling mediators such as p38-MAPK and epidermal growth factor receptor (EGFR). This study aimed to investigate the anti-inflammatory and anticancer efficacy of the scorpion venom peptide Smp24 (SMP24) and its bimetallic nano-conjugates, SMP24-ZnOCuO, and SMP24-AgCuO, in a murine model of solid Ehrlich carcinoma (SEC).Experimental approach Solid tumors were induced in female Swiss albino mice via subcutaneous injection of 2.5 × 106 Ehrlich carcinoma cells. After tumor establishment (∼50 mm³), mice were randomly assigned to nine groups (n = 6/group), including controls, treatment groups, and a cisplatin reference group. Treatments were administered intraperitoneally every 48 hrs for 2 weeks. At the end of the experiment, blood, tumor tissues, and organs were collected for biochemical, cytokine, molecular, histopathological, and immunohistochemical analyses.Key findings SEC-bearing mice showed significant increases in body weight, organ indices, liver enzymes, and creatinine levels, alongside elevated pro-inflammatory cytokines (IL-6, IL-8) and reduced anti-inflammatory cytokines (IL-4, IL-10). Histopathological alterations and increased expression of p38 and EGFR were also observed. Treatment with SMP24 and its nano-conjugates significantly restored cytokine balance, reduced organ toxicity markers, and improved tissue architecture. Notably, SMP24-AgCuO demonstrated superior efficacy, markedly suppressing IL-6 and IL-8, enhancing IL-4 and IL-10, and significantly downregulating p38 and EGFR expression compared to cisplatin.Conclusions SMP24-conjugated bimetallic nanocarriers, particularly SMP24-AgCuO, exhibit potent anti-inflammatory and anticancer effects through modulation of the EGFR/p38-MAPK signaling axis. These findings highlight their potential as a targeted and safer therapeutic strategy for managing tumor-associated inflammation and cancer progression.