According to a WHO estimate, cancer remains the prominent source of death and a major barrier to increasing longevity, accounting for 10 million deaths in 2020. By 2040, it is anticipated that there will be 29.5 million newly detected instances of cancer annually and 16.4 million fatalities due to cancer [1], [2], [3]. Globally, cervical cancer ranks third among fatalities from cancers that affect women [4]. Cervical cancer begins to strike people at earlier ages. As per Olusola et al. [5], it is an issue that cannot be disregarded. Through intercourse, HPV, the primary basis of cervical cancer, infects the cervix's epithelial cells. Several research investigations have demonstrated that a high-risk HPV infection is linked to over 90% of cervical cancer cases and over 70% of cases that expand to encompass additional bodily areas [5]. The primary issue with these treatments, which cause the body to lose both good and damaged cells, is that they have detrimental side effects, making them unsuitable even with advanced therapies [6]. The limited solubility, incapacity to enter tumors, indiscriminate focusing on, and severe harm to the immune system and other organs of conventional medicines limit their effectiveness and decrease the chance of survival [7]. Despite new medical discoveries and innovations in technology, even now, one of the worst illnesses is cancer [8].

In recent times, enhanced efficacy among anti-microbial, biomedical, environmental, and therapeutic uses has been achieved by nanomaterials that are engineered through morphological alterations. Green synthesis, which uses natural substances instead of physical or chemical synthesis agents to create nanoparticles, is an exciting development in nanotechnology [9]. It has been discovered that the traditional methods of creating nanoparticles (physical and chemical) are expensive, involve hazardous chemicals, produce less stable nanoparticles, and are not ecologically friendly [10]. In order to generate precious metal nanoparticles, natural phytochemical pigments, and enzymes have all been used in the investigation of the green synthesis approach [11]. The ability of bimetallic nanoparticles to blend the qualities of two metals has been attributed to them [12]. Once associated with monometallic nanoparticles, bimetallic nanoparticles (BM-NPs) have improved characteristics.

BM-NPs arise from the joining of atoms from two distinct metals into the same nanoparticle. According to several reports, BM-NPs can have unique characteristics due to the combined impacts of two or more metals as well as the collection of attributes associated with the presence of two or more different metals [13], [14]. Because of their industrial, medical, and environmental uses, bimetallic silver (Ag) and zinc oxide (ZnO) nanoparticles have become increasingly important. There have been reports of bimetals, which are composites of two distinct metals, having anticancer, thrombocytic, and anti-inflammatory properties [11], [15], [16], [17], [18]. The individual metals contribute different qualities which, when coupled yield a more potent antitumor effect. For instance, the synergism of the silver and zinc ions—silver triggers apoptosis, whereas zinc enhances ROS production—was given credit for the anticancer potential of Ag-Zn nanocomposites. This was further highlighted by the finding that cancer cells responded significantly more strongly to BNP therapy than they did to individual metals [19]. Similarly, the genotoxic properties of CuO nanoparticles and the apoptosis and ROS-inducing activities of ZnO nanoparticles were combined to create a hybrid nanocomposite with increased anticancer efficacy [20]. Therefore, an increasing number of herbal products are being utilized to create nanomaterials these days. Using an aqueous extract of Crocus sativus (saffron stigmas) as a reducing, stabilizing, and capping agent, we synthesized bimetallic silver and zinc oxide nanocomposites (Ag/ZnO NCs) for the first time.

The stigma of the saffron plant includes a number of active phytochemicals, including carotenoids. The medicinal benefits of C. Sativus includes antibacterial, anti-tumor, antioxidant, anxiolytic, neuronal protection, anti-ischemic, and protection against DNA damage actions [21], [22], [23]. In this investigation, a straightforward and environmentally friendly process was used to create bimetallic Ag@ZnO NCs utilizing C. sativus extract. The produced bimetallic NCs have been studied by X-ray diffraction (XRD), Fourier transform infrared spectroscopy, field emission gun scanning electron microscopy (FE-SEM), and energy dispersive analysis of X-rays (EDX). Further, human cervical carcinoma (HeLa) has been used to assess the antitumor activity of these biosynthetic bimetallic Ag@ZnO NCs.

The PI3K/AKT/mTOR pathway represents one of several signaling cascades that regulate crucial cellular and molecular processes crucial for the initiation, invasion, and metastasis of tumors [24]. Research suggests that the upregulation of the PI3K and AKT components in this pathway is linked to various human tumors, such as breast, ovarian, endometrial cancers, and malignant gliomas. Moreover, Schwarz et al. (2012) reported that the activation of the PI3K/AKT pathway is correlated with an inadequate response in cervical cancer [25]. According to their findings, cervical cancers may potentially be treated by targeting the PI3K/AKT/mTOR signaling system through these biosynthetic bimetallic Ag@ZnO NCs. Hence, in the present investigation, we developed biosynthesized bimetallic Ag@ZnO NCs using a plant extract from C. sativus and evaluated their effectiveness against a cervical cancer cell line.