![]() reported an IC 50 (the concentration of NPs caused 50% mortality) of 1.71 μg/mL for CuO NPs against A375 cancer cells 55. In another study, CuO NPs were synthesized using a green method these NPs inhibited mRNAII expression in A549 cancer cells and stimulated apoptosis 54. Biogenic ZnO NPs were eco-friendly synthesized using Cardiospermum halicacabum and Mangifera indica leaf extracts, and they illustrated good antitumor properties against A375 and A549 cells at a concentration of 50 μg/mL, respectively 4, 53. Metal oxide NPs such as zinc oxide (ZnO) and copper oxide (CuO) demonstrated diverse biological applications these NPs were highly compatible with normal cells in the body. Typically, the synthesis of multimetallic and bimetallic NPs is costly and time-consuming, and may include toxic or hazardous substances. Additionally, biogenic copper and zinc oxide NPs were synthesized in 20, and their anticancer activities were evaluated against T98G human glomerular superficial cell and cervical cancer, respectively 51, 52. In 2019, silver/palladium bimetallic NPs were synthesized using Terminalia chebula fruit extract, and their antitumor properties were evaluated against A549 50. In another study, the gold(i)-BODIPY-imidazole bimetallic complex demonstrated good anti-proliferative activity against breast, colon, and prostate cancer 49. Pt/Pd bimetallic NPs were synthesized using Dioscorea bulbifera extract, and gold-silver bimetallic NPs were synthesized using Stigmaphyllon ovatum leaf extract their anticancer activity against HeLa cells was also investigated 47, 48. synthesized silver/gold bimetallic NPs with the aim of reducing the nano metallic toxicity of silver, and evaluated their antitumor activity on melanoma cancer cells 46. In recent decades, the antitumor activity of different biogenic and non-biogenic bimetallic NPs has been evaluated 43, 44, 45. These integrated NPs have more reactive sites, increased efficiency, and greater stability 41, 42. On the other hand, bimetallic and multimetallic NPs have shown unique physicochemical properties with synergistic effects and high functionality 40. The therapeutic effects of NPs depend on the particle size, the culture time of the target cell, the amount of metal in the targeted cell, and their physicochemical properties 36, 37, 38, 39. Nanoparticles (NPs) have gained interest of scientists in the field of nanomedicine 29, 30, 31, 32, 33, 34, 35, 36. Rapid and targeted penetration in cancer cells can prevent the spread of disease to other tissues, and thus control the cancer. Indeed, rapid proliferation of cancer cells and necrosis of normal cells in the body are prominent features of cancer cells and side effects of current cancer therapy. Therapeutic methods based on the application of encapsulated herbal compounds in nanomaterials 27, hyperthermia, targeted delivery of genes or anticancer drugs to the cells/tissues have resulted in efficient cell death of cancer cells in the targets 28. The biomedical potentials of various secondary metabolites such as phenolic compounds, flavonoids, glycosides, terpenoids and aldehydes have been evaluated 24, 25, 26. Different evaluations have been performed on the anticancer properties of various nanoscaled structures, composites, RNAs, and polymers 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23. Despite some advantages, conventional chemotherapy is discouraging to invest more in drug discovery and/or drug delivery systems due to some drawbacks such as poor bioavailability of drugs to tumor tissues, adverse side effects, low therapeutic indices, high dose requirements, non-specific targeting, and multidrug resistance 8, 9. Currently, the most common treatments for cancer are surgery, radiation therapy, immunotherapy, hormonal therapy, and chemotherapy 5, but recently many researchers have turned to nanomaterials and herbal anticancer drugs 6, 7. One of the reasons for the high mortality rate of patients with lung cancer and melanoma is the uncontrolled growth of cancer cells in the lung and skin tissue, metastasis and spread to sensitive organs (such as the brain). Cancer cells release a variety of factors into their environment which can change the function of cells in the tumor microenvironment 4. One of the most important features of the cancer cells compared to somatic cells is their ability to replicate and spread to different parts of the body. Lung cancer and melanoma are the most deadly ones. Cancer as one of the most aggressive diseases kills more than ten million people every year 3. Cancer can cause the unregulated cell growth with high potential to invade and spread to other cells and tissues of the body by the lymph system and blood via a metastatic process 1, 2.
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