Hesperidin is a flavonoid glycoside with proven therapeutic activities for various diseases, including cancer. However, its poor solubility and bioavailability render it only slightly absorbed, requiring a delivery system to reach its therapeutic target. Hesperidin loaded on gold nanoparticles (Hsp-AuNPs) was prepared by a chemical synthesis method. Various characterization techniques such as UV-VIS spectroscopy, ftiR, XRD, feSeM, teM and eDX, Zeta potential analysis, particle size analysis, were used to confirm the synthesis of Hsp-AuNPs. The cytotoxic effect of Hsp-AuNPs on human breast cancer cell line (MDA-MB-231) was assessed using MTT and crystal violet assays. The results revealed significant decrease in proliferation and inhibition of growth of the treated cells when compared with human normal breast epithelial cell line (HBL-100). Determination of apoptosis by fluorescence microscope was also performed using acridine orange-propidium iodide dual staining assay. The in vivo study was designed to evaluate the toxicity of Hsp-AuNPs in mice. The levels of hepatic and kidney functionality markers were assessed. No significant statistical differences were found for the tested indicators. Histological images of liver, spleen, lung and kidney showed no apparent damages and histopathological abnormalities after treatment with Hsp-AuNPs. Hsp-AuNPs ameliorated the functional activity of macrophages against Ehrlich ascites tumor cells-bearing mice. The production of the pro-inflammatory cytokines was also assessed in bone marrow-derived macrophage cells treated with Hsp-AuNPs. The results obviously demonstrated that Hsp-AuNPs treatment significantly inhibited the secretion of IL-1β, IL-6 and TNF. The burden caused by cancer to the global public health has been markedly increasing, as evidenced by an estimate of 9.6 million mortalities in 2018 (around one sixth of the overall worldwide mortalities), around 70% of which being recorded in nations with low to middle income 1,2. The most frequently diagnosed type of cancer in females is breast cancer, being the reason for more than one tenth of annual newly diagnosed cases and the second cause of mortality. In Iraq, breast cancer occupies the second rank, following cardiovascular diseases, as a major cause of mortality (23% of cancer-related deaths in women) 3. Direct administration of the available chemical drugs is generally problematic, while these chemicals often exert toxicity and unwanted side effects to the patient's

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