In Asian and African cultures, medicinal plants have been used as traditional remedies for thousands of years. In Western countries, numerous plants are consumed because of their multiple health advantages. The WHO indicates that certain countries continue to rely on plant-based treatments as their primary form of medicine, while developing nations are harnessing the advantages of naturally derived substances for therapeutic applications (Zahra et al., 2020; Bajpai et al., 2024). Numerous questions have been raised regarding the effectiveness of herbal medicines in enhancing the body’s immune cells against cancer. Consequently, a number of herbal formulations have been developed to fight malignant cells without endangering healthy cells in the body, based on documented information on the intricate synergistic interaction of several phytochemicals with anticancer potential (Craig, 1999). Herbal remedies and medicinal plants play an important role in primary healthcare systems, particularly in rural areas, because conventional anticancer treatments are extremely expensive and out of reach for low-income populations. Herbal remedies have been helpful in cancer prevention and treatment because of their ability to suppress hormones and enzymes that activate cancer, boost the DNA repair mechanism, induce antioxidant action, and improve immunity, all of which contribute to anticancer effects (Greenwell and Rahman, 2015). Several medicinal plants are currently being studied in clinical trials to determine their potential anticancer effects (Figure 1). Researchers have also conducted extensive research on the phytochemicals found in plants (Solowey et al., 2014). Because of the side effects caused by conventional cancer treatments, some patients are turning to complementary and alternative medicine in an attempt to identify a more effective treatment (Gielecińska et al., 2023).

Several studies have utilized traditional material medica literature as a basis for cancer medication development. To develop promising candidates with anticancer properties, it is necessary to thoroughly understand the many phytochemicals found in plants and how they work together (Merina et al., 2012; Shaikh et al., 2016). The capacity to alter one or more particular molecular processes has led to the isolation and identification of several novel chemopreventive drugs. A different and supplementary approach to cancer prevention and/or therapy may be developed as a result of the identification of useful herbs and the clarification of their underlying mechanisms. Several plant-derived anticancer drugs, including vinblastine, camptothecin, and taxol, have been isolated and characterized from different plant species (Cragg and Newman, 2005). Conventional therapeutic options have demonstrated inadequate results in meeting the essential criteria for effective cancer treatment, leading to a significant interest in plant-derived anticancer agents, which are both cost-effective and safe because of their natural nature. Thus, there is potential for the extended use of plant formulations or herbal extracts for anticancer treatment. In recent decades, herbal treatments have been widely adopted, significantly influencing both the global healthcare systems and the international commerce of herbal products. Medicinal plants have been confirmed to play a significant role in the healthcare systems of a substantial portion of the global population (Antonio et al., 2014). Recently, the utilization of plants and plant-derived phytomedicines has surged significantly in developed countries such as the USA owing to their lower toxicity and natural origin. Numerous medicinal plants are traditionally utilized for the treatment and prevention of malignancies worldwide, including India. The promising and rapidly increasing application of plant derived compounds in cancer therapy necessitates comprehensive scientific investigation of diverse and biologically relevant phytochemicals, alongside their detailed anticancer mechanisms and clinical studies, which could represent a compelling area for future cancer research (Shukla and Mehta, 2015).

Despite significant efforts in preclinical studies, the translation of phytochemicals for human use has seen modest success. Poor transport of potential natural agents to the target site is likely the primary reason for clinical failure. This may be attributed to the agents’ inadequate water solubility and chemical instability inside the biological milieu. Moreover, the inadequate pharmacokinetic properties of secondary metabolites of plants, resulting from rapid metabolism, limited solubility, and instability, cause many issues related to toxicity, inefficacy, and diminished tissue distribution. Therefore, it is critical for cancer treatment to find new and improved delivery systems that can overcome these obstacles (Wei et al., 2019).

Given the incredible progress that has been made in the field of nanotechnology, it should not come as a surprise that researchers have shown an increasing interest in the topic in recent years. Owing to its intrinsic versatility, nanotechnology is used in a wide range of fields such as electronics, sensors, optics, chemistry, pharmaceuticals, cosmetics, biomedical sciences, and environmental science. There are variations in the characteristics of nanoparticles (NPs) owing to differences in their chemical composition, shape, size, and controlled release. These discrepancies frequently stem from the synthesis process, which is affected by multiple factors. The goal of modern nanoparticle production is to achieve nanoscale dimensions while simultaneously making sure the synthesis method is easy to understand, inexpensive, eco-friendly, and adaptable to many uses (Zhang et al., 2016; Almatroudi, 2020). For the most part, metal nanoparticles, which include silver, gold, and platinum NPs, are rather small, measuring approximately 50 nm, and possess a high surface area. They possess the capability to traverse capillaries within tissues and cells because of their small size. Their enormous surface area, coupled with their capacity for chemical modification, enables them to accommodate a substantial quantity of drugs. In this context, metal nanoparticles have been utilized for the regulated release of drugs in cancer therapy (Patra et al., 2018). Although certain metals are preferred to be inert, bioaccumulation and toxicity may occur. Conversely, a significant benefit of metal nanoparticles is their capacity to effectively absorb light energy and transform it into heat. Consequently, certain agents can be utilized in hyperthermic tumor therapy, wherein photostimulation delivers thermal energy, rendering this treatment very specific (Ahlawat et al., 2020).

Owing to their unique physiochemical and biological intrinsic features, silver nanoparticles (AgNPs) have been used in the pharmaceutical, aerospace, food, and biomedical sectors. They are characterized by high electrical conductivity, biological peculiarities, and excellent optical characteristics (Huy et al., 2020). The AgNPs demonstrated utility in industrial and health-related goods, including the coating of medical equipment, biosensors, bio-imaging, and as antimicrobial, antiparasitic, antiviral, anticancer agents, and drug delivery systems, among various other applications (Shanmuganathan et al., 2019; Sakthi et al., 2022; Kaushal et al., 2023). Owing to their high surface/volume ratio, ease of production, customizable surface chemistry and functionalization, and excellent penetration and traceability throughout the body, silver nanoparticles have been extensively investigated and used in therapies (Marassi et al., 2018). AgNPs are widely used in preclinical studies using different cancer cell models owing to their inherent antitumor potential, but some recent scientific studies have sought to enhance antitumor efficacy by combining AgNPs with conventional anticancer drugs, especially when used in combination with phytocompounds employed in their synthesis (Morais et al., 2020; Gomes et al., 2021). AgNPs offer a novel approach for cancer therapy through nanotechnology as a potential nanoproduct for cancer treatment. Their ability to selectively block the respiratory chain in the mitochondria, which produces reactive oxygen species (ROS) and damages DNA, is one of their proven anticancer properties (Ovais et al., 2016). The production of AgNPs is accomplished by converting silver ions into nanoscale, extremely tiny materials through the application of nanotechnology (Yesilot and Aydin, 2019). Compared to chemical and physical approaches, biogenic (green) methods offer more environmentally friendly ways to convert bulk silver ions into AgNPs. The use of plants in the biogenic synthesis of AgNPs is characterized by cost-effectiveness, reduced risks to humans and the environment, and ease of execution. Nanoscale silver nanoparticles (AgNPs) exhibit novel physicochemical features and can enhance distinctive biological functions (Wei et al., 2015; Kah et al., 2023).

The anticancer capabilities of AgNPs can be explained by a number of processes, as stated in relevant research. It is clear that cancer cells exhibit an enhanced permeation and retention effect (EPR), which causes an influx of AgNPs, which eventually kill cancer cells or at least repress their uncontrolled growth. Furthermore, AgNPs function by modulating signaling pathways, leading to either the induction of early apoptosis or inhibition of rapid tumor cell proliferation. Moreover, certain studies indicate that the stimulation of p53, caspase-3, and p-ErK1/2 by AgNPs ultimately induces apoptosis and modulates cell division through a sequence of intracellular events (Gurunathan et al., 2015; Buttacavoli et al., 2017; Bethu et al., 2018).

Numerous studies have demonstrated that treatment of tumor cells with green-synthesized AgNPs induces ROS, which causes cellular damage (Minai et al., 2013; Ratan et al., 2020). In an experimental finding, researchers ascribe the anticancer effect of green-synthesized AgNPs to the active generation of ROS. Elevated ROS levels affect cell signaling pathways that are crucial for apoptosis activation (Hembram et al., 2018). Existing literature indicates that green-synthesized AgNPs induce ROS production, which eventually results in apoptosis and cell death.

Buttacavoli et al. studied the effect of AgNPs on the SKBR3 breast cancer cell line using advanced methods and procedures. These results provide a definitive understanding of how AgNPs work against human cancer cell lines (SKBR3) to prevent cancer. They documented substantial suppression of cell motility and inhibitory effects on metalloproteinases (MMPs). Notable morphological alterations in cancer cells were observed following treatment with AgNPs, including shrinkage, shape irregularity, cytoplasmic blebbing, alterations in intracellular vacuole morphology, and chromatin condensation. Alongside these alterations in cancer cells, the generation of ROS induces oxidative stress and cellular apoptosis. Additionally, findings documented the elevated levels of LC3-II, ATG7, beclin-1, and ATG5, alongside the decreased levels of HSP90, AKT, P62, and p-AKT autophagic markers (Buttacavoli et al., 2017; Raja et al., 2020). Research indicates that cancer cells exhibit an enhanced permeability and retention (EPR) effect (Maeda, 2010), resulting in the increased uptake of nanosilver and the production of more toxic silver ions. By destroying essential biomolecules, the oxidative stress produced in tumor cells disrupts numerous physiological processes and molecular pathways, leading to the destruction of essential cellular organelles, ultimately resulting in the death of tumor cells (Datkhile et al., 2023; Ullah et al., 2024). The formation of new blood vessels by vascular endothelial growth factor (VEGF) enhances tumor progression and metastasis (Pathak et al., 2024). Studies indicate that AgNPs influence the activity of VEGF, hence functioning as an anti-angiogenic agent (Palanisamy et al., 2024). In addition to reducing the cytotoxic effects of chemotherapy on healthy tissues, silver nanomaterials serve as carrier vehicles for the therapeutic anticancer payload (drugs), increasing the effectiveness and potency of anticancer medications and preventing cancer cells from developing resistance to them (Karuppaiah et al., 2020; Sofi et al., 2022). Lin et al. revealed that AgNPs function as anticancer agents by inducing autophagy in cancer cells via activation of the PI3K pathway. Moreover, they noted that the suppression of autophagy by autophagic inhibitors, such as wortmannin, increased the efficiency of cancer cell eradication in a mouse melanoma cell model (B16 cell lines) (Lin et al., 2014). Jia et al. assessed the impact of AgNPs on human colon cancer HCT116 cells and observed that increasing concentrations of AgNPs diminished cellular activity while elevating intracellular ROS levels. Protein and gene expression analyses demonstrated that AgNPs elevated p38 protein phosphorylation levels and upregulated the expression of Bax and p53. Moreover, Bcl-2 expression is downregulated and the levels of p21 upregulated, which expedites cellular apoptosis (Jia et al., 2020). Nonetheless, green AgNPs may activate some of the aforementioned pathways and potentially other mechanisms because they can be naturally stabilized with bioactive organic molecules during their formation.

To achieve green synthesis of silver nanoparticles (AgNPs), it is possible to make use of live organisms, which represent the kingdom of the biological system. In addition to being essential for the production of food and nutrition, living organisms are also critical for green synthesis. Since many plants have a large biomass, scientists prioritize using them to carry out green synthesis of AgNPs because of their molecular arsenal and biomass richness (Shafey, 2020). The primary and secondary metabolites of plants influence their response to stress factors and survival agents making them principal bioreactors and molecule providers for green synthesis (Jha et al., 2009). Metal ion reduction occurs because of the occurrence of metallic counterparts and the stabilization of the surface of the AgNPs (El-Seedi et al., 2019). Plant derived molecules that contribute to this process include citric acid, amino acids, phenolic compounds, terpenoids, heterocyclic compounds, enzymes, peptides, polysaccharides, saponins, and tannins (Thakkar et al., 2010; Shah et al., 2015; Yosri et al., 2021; Shah et al., 2024). The green synthesis of AgNPs can be achieved by using either the entire plant or its organs or tissues, or extracts from these, along with other plant components (such as seeds, leaves, bark, roots, and fruits) to create nano-objects that exhibit a variety of characteristics (Roy, 2021; Shiraz et al., 2024) (Figure 2).

A plant extract was amalgamated with a metal precursor solution under diverse reaction conditions to synthesize nanoparticles (Malik et al., 2014). Nanoparticle synthesis, productivity, and stability are influenced by the reaction variables regulating the plant extract, including the metal salt quantity, phytochemical quantity, solution temperature, pH level, and phytochemical category (Li et al., 2011). In contrast to bacteria and fungi, which require extended incubation periods, the phytochemicals present in plant extracts have a greater propensity to reduce metal ions within a shorter timeframe. Consequently, plant extracts are regarded as excellent candidates for the biosynthesis of metallic nanoparticles. Plants possess diverse amounts of phytochemicals, which are significant elements in nanoparticle synthesis. Nanoparticle bioreduction mostly involves plant-based natural products such as sugars, carboxylic acids, polyphenols, terpenoids, ketones, and aldehydes (Makarov et al., 2014; Thatyana et al., 2023).

Phytoconstituents of the plant serve as exceptional reducing and stabilizing agents. The flower extract of Loni cera hypoglauca functions as a reducing and capping agent in the manufacture of AgNPs and exhibits anticancer action (Jang et al., 2016). Leaf extract of Artocarpus integer was utilized to produce silver nanoparticles (AgNPs), resulting in spherical nanoparticles ranging from 5.76 nm to 19.1 nm in size (Majeed et al., 2019). The extract of Catharanthus roseus utilized for the synthesis of AgNPs exhibited indole-type alkaloids, which function as reducing and stabilizing agents (Al-Shmgani et al., 2017). Greenly produced silver nanoparticles (AgNPs) utilizing leaf extracts from Clitoria ternatea and Solanum nigrum have shown antibacterial efficacy against nosocomial infections. The synthesis of nanoparticles was validated by UV, FTIR, SEM, and XRD analyses (Krithiga et al., 2015). The pulp extract of Abelmoschus esculentus (L.) was utilized to synthesize AgNPs measuring 3–11 nm, which exhibited anticancer and antibacterial properties (Mollick et al., 2019). In addition to this, several other research studies demonstrate the advanced development of nanoparticles via the green synthesis process and their prospective applications in medicine (Jain et al., 2021).

Research on biogenic NPs using plant materials has become an emerging field because of the growing use of NPs in the management and treatment of cancer. Traditional methods of producing nanoparticles (NPs) sometimes require the use of harsh chemical reducing agents, which are not only expensive and complicated, but also have the potential to generate highly harmful byproducts. Consequently, there is an undeniable need for more cost-effective and environmentally benign alternative methods that can mitigate the risk of environmental contamination. This section summarizes the plant-based AgNPs currently utilized in anticancer therapy and examines their use across diverse cancer types (Table 1). Figure 3 depicted the anticancer mode of action of green synthesized AgNPs as therapeutic and cytotoxic agent.

Despite the prevalence of gastrointestinal cancer, the existing diagnostic and treatment methods are insufficient (Zhao et al., 2020). Many metallic nanoparticles (MNPs), particularly AgNPs, have been extensively studied for various medicinal uses, including cancer. They have the ability to overcome the difficulties posed by traditional chemotherapy and have a major effect on the overall survival of patients with gastrointestinal cancer. AgNPs with targeted ligands enhanced the localization of tumor energy deposition, improved solubility and stability, and exhibited specific targeting characteristics. In recent years, numerous researchers have demonstrated and elucidated the cytotoxicity of AgNPs, developed via green technologies, in different gastrointestinal cancer cell lines (Roshani et al., 2023). This section presents an overview of green-manufactured AgNPs and their advancements in targeted gastrointestinal cancer therapy in preclinical research.

Arul and Kothai produced AgNPs using the whole plant extract of Abutilon hirtum (Lamp), which were evaluated for their cytotoxic efficacy against HepG2 cell lines. The MTT experiment demonstrated that the produced AgNPs had a substantial cytotoxic effect on HepG2 cell lines (Arul and Kothai, 2023). Guo et al. synthesized AgNPs using Berberis thunbergii leaf extract, demonstrating great selectivity and increased cytotoxicity against three different pancreatic cancer cell lines (PANC-1, AsPC-1, and MIA PaCa-2). Furthermore, the IC₅₀ values of the AgNPs were determined to be 259, 268, and 141 μg/mL when tested against the PANC-1, AsPC-1, and MIA PaCa-2 cell lines specifically (Guo et al., 2022). Likewise, the extract of Eucalyptus camaldulensis leaves has been employed for the biosynthesis of AgNPs. This study examined the anticancer efficacy of colloidal silver nanoparticles derived from Eucalyptus camaldulensis leaves against human colon cancer Caco-2 cells. The cytotoxicity experiment on the Caco-2 cell line demonstrated both a dose- and time-dependent effect of AgNPs. After 48 h of exposure, a low concentration (5 μg/mL) decreased cell viability to 50%. Exploring new avenues for treating human colon cancer Caco-2 could be facilitated by the strong cytotoxicity of AgNPs at low concentrations (Zein et al., 2020).

Shaniba et al. produced AgNPs using leaf extracts from Manilkara zapota (L.). This study examined the cytotoxic effects of biosynthesized nanoparticles on HCT116 colon cancer cells. After 72 h of treatment, AgNPs dose-dependently and selectively suppressed the development of colorectal cancer HCT116 cells, with an IC₅₀ value of 8 μg/mL, while having no effect on the growth of normal cell lines. Using scanning electron microscopy and fluorescence, AgNP-mediated induction of apoptosis was confirmed. The treatment of cells with AgNPs in conjunction with cisplatin resulted in the overproduction of ROS, a decrease in mitochondrial membrane potential, overexpression of apoptotic-related genes including PUMA, caspases, and BAX, and an increase in PARP cleavage (Shaniba et al., 2019). AgNPs were biosynthesized using the leaf extract of Moringa oleifera. The cytotoxicity of these biogenic AgNPs was assessed using the MTT assay in colon cancer cells (HTC116 and SW480). Biogenic AgNPs enhanced the cytotoxic effects in a dose-dependent manner as the dose increased from 3.12 to 100 μg/mL. The IC₅₀ value for M. oleifera-AgNP against HTC116 cells was 70 μg/mL, but that for SW480 cells was 100 μg/mL. M. oleifera AgNPs reduced the expression of the CTNNB1 and LRP6 genes, although the expression of the LRP5 gene increased in both cell lines. Following treatment, APC gene expression was diminished in SW480 cells and augmented in HTC116 cells. Overall findings suggest that AgNPs produced by M. oleifera extract may effectively prevent colon cancer progression by regulating Wnt/β-catenin signaling (Althomali et al., 2022). Likewise, Susanto et al. demonstrated the antiproliferative efficacy of AgNPs biosynthesized from Moringa oleifera in HT-29 cells. MTT assay results indicated that AgNPs produced from Moringa oleifera leaf extract significantly reduced HT-29 cell viability and proliferation in a dose-dependent manner. AgNPs also decreased the expression of cell cycle- and proliferation-associated genes including Ki-67, Wnt, β-catenin, and Cyclin D1. Moreover, biogenic AgNPs decreased the expression of metastasis-associated genes, including TGF-β and Snail, recognized as inducers of metastasis (Susanto et al., 2024).

Usmani et al. manufactured AgNPs from the seed extract of Nigella sativa and evaluated their efficiency against hepatocellular carcinoma using HepG2 cell lines. Morphological changes and cell viability experiments in HepG2 cells indicated that N. sativa AgNPs efficiently limited cell growth in a dose-dependent manner. It has been demonstrated that N. sativa AgNPs have considerable anticancer potential against human hepatocellular carcinoma, as evidenced by the disintegration of apoptotic nuclei and the resulting increase in ROS generation. This was accomplished without any effect on normal cells (Usmani et al., 2019). Moreover, AgNPs biosynthesized from the leaf extract of Vitex negundo reduced proliferation and caused apoptosis in HCT15 colon cancer cells. AgNPs have substantial antiproliferative effects on human colon cancer cells in vitro because of their weak chemical interactions with leaf extract components. According to these findings, AgNPs induced apoptosis by causing G0/G1 cell cycle arrest. Cells treated with AgNPs exhibited DNA damage and increased oxidative stress indicators, which accounted for the cytotoxic effects (Prabhu et al., 2013). Venkatadri et al. have simultaneously employed aqueous extracts of the rhizomes of Zingiber officinale and Curcuma longa for the green production of silver nanoparticles (AgNPs). This study examined the cytotoxic effects of biosynthesized AgNPs on HT-29 colon cancer cells. Based on the MTT experiment, AgNPs exhibited strong anticancer action against HT29 cells, with an IC₅₀ value of 150.8 μg/mL (Venkatadri et al., 2020). In a similar manner, Jain et al. developed silver nanoparticles utilizing various species of the rhizome of Curcuma longa. All nanoparticles derived from the rhizome extracts repressed the viability of HT-29 cells to varying degrees. HT-29 cells exhibited sensitivity to the formulated nanoparticles, which elicited increased cytotoxicity against cancer cells (Jain et al., 2023). Additionally, silver nanoparticles were synthesized using the aqueous leaf extract of Zingiber officinale. The cytotoxicity of AgNPs was evaluated using the MTT assay on pancreatic cancer cells. Biogenic silver nanoparticles exhibited significant anti-pancreatic cancer effects against PANC-1, AsPC-1, and MIA PaCa-2 cells, while demonstrating minimal cytotoxic action towards normal cell lines (Wang et al., 2021). The synthesis of AgNPs using a green approach utilizing Photinia glabra fruit extract has been documented. The antiproliferative effects of the synthesized AgNPs on Eca-109 cells were evaluated. The experimental data indicate that PG-AgNPs exhibited significant cytotoxicity against esophageal cancer cells, with IC₅₀ values below 20 μg/mL (Namulinda et al., 2023).

Unregulated cell proliferation in female reproductive organs is the hallmark of gynecological cancers, which can be characterized as cervical, ovarian, vaginal, uterine, and vulvar malignancies. These malignancies pose considerable risks to women’s health, affecting their lifespans, quality of life, and fertility. More than 116,000 new cases of gynecological malignancies were reported in 2024 (Keyvani et al., 2022). Gynecological malignancies represent a significant worldwide health concern for women and are characterized by elevated incidence rates and an urgent need for enhanced prognostic outcomes (Suneja and Viswanathan, 2020). Current therapeutic techniques include surgical intervention, chemotherapy, radiation, and immunotherapy. Although surgery is mostly useful for solid tumors in their early stages, there is a chance that the tumor will not be completely removed and that it may spread or be implanted (Chen et al., 2019). Chemotherapy is associated with cytotoxicity and reduced bioavailability, constraining its extensive use (Akbarali et al., 2022). There is a limited therapeutic applicability for immunotherapy, and it is not appropriate to tumor forms that have immune suppression or exclusion-like properties (Tan et al., 2020; Zhou et al., 2025).

Recently, nanomedicine has made it possible to create tailored cancer treatments, addressing the primary challenge of existing systemic treatment methods. Combination therapy mediated by nanoparticles can be utilized in conjunction with efflux pump inhibitors, pro-apoptotic substances, and MDR-targeted siRNA (Mignani et al., 2015). AgNPs exhibit potential cytotoxicity in cancer cells and have demonstrated significant anticancer efficacy (Sriram et al., 2010). AgNPs can trigger apoptosis and autophagy, two essential processes in the breakdown of different tumor cell types (Zhang and Gurunathan, 2016). Inhibition of autophagy amplifies the anticancer efficacy of AgNPs (Lin et al., 2014). Additionally, AgNPs can cause apoptosis and suppress the proliferation and survival of cells in numerous cancer cell lines, such as breast, cervical, lung, ovarian, and prostate cancer (Gurunathan et al., 2015; Yuan and Gurunathan, 2017; Yuan et al., 2017; Darabdhara et al., 2019). As a result, using nanoparticles to treat gynecological cancers is a cutting-edge treatment with enormous promise. Rajkuberan et al. demonstrated the quick synthesis of silver nanoparticles using aqueous latex extract of Euphorbia antiquorum L to assess its anticancer effectiveness in the cervical cancer HeLa cell line. Phyto-fabricated AgNPs have demonstrated considerable antitumor efficacy against human cervical carcinoma cells (HeLa). Microscopical and preliminary biochemical investigations showed that biosynthesized AgNPs cause significant cytotoxicity in HeLa cells with an IC₅₀ value of 28 μg (Rajkuberan et al., 2017). Aboelmaati et al. conducted another work that generated biogenic and biocompatible silver nanoparticles (AgNPs) from the non-edible stem of Hibiscus sabdariffa. This study examined the antitumor efficacy of biogenic AgNPs against the ovarian cancer cell lines WI-38 and SK-OV-3. Biogenic AgNPs demonstrated apoptotic and anti-ovarian cancer effects with an IC50 value six times greater than that of the normal cell line (Aboelmaati et al., 2021).

Vasanth et al. synthesized green silver nanoparticles (AgNPs) using Moringa oleifera stem bark extract. Electron and atomic force microscopy images were obtained to examine the surface morphology of the AgNPs. The impact of the manufactured AgNPs was assessed in human cervical cancer cells (HeLa), and cell morphology was analyzed using nuclear staining dye, which showed remarkable cytotoxic effects. The efficacy of green produced AgNPs was examined using fluorescence activated cell sorting (FACS) and demonstrated to trigger apoptosis via reactive oxygen species (ROS) production in HeLa cells (Vasanth et al., 2014).

Malignant Melanoma, the most fatal variant of skin cancer, is an aggressive and resilient tumor that originates from melanocytes (Castro-Pérez et al., 2023). Melanoma has become a major global public health problem in recent years due to its constantly rising prevalence (Janda and Sinclair, 2022). Recent research has shown that the use of specific nutrient-rich food ingredients can prevent their spread. Although conventional therapies may be applicable in the initial phases of this condition, metastatic melanoma persists as an uncontrolled disease owing to its capacity to evade drug-induced apoptosis (Pellegrini et al., 2021; DeWane et al., 2022). Recently, treatments based on nanomaterials have garnered considerable attention. Silver nanoparticles (AgNPs) possess unique physicochemical and biological properties, leading to diverse biomedical applications (Islam et al., 2021; Naganthran et al., 2022). AgNPs are mostly produced using physicochemical techniques. These conventional methods are generally hazardous, unstable, expensive, lengthy, and detrimental to biodiversity. The manufacturing of nanoparticles must be biocompatible, economically viable, and environmentally friendly for application in the pharmaceutical sector (Ashique et al., 2022). Among the biological methods for synthesizing AgNPs, the synthesis of plant extracts is notably favored owing to its enhancement of herbal therapeutic properties, facilitation of the prolonged release of active constituents, and reduction of the necessary dosage. The biosynthesis of AgNPs presents a promising avenue mostly utilized for antibacterial and anticancer therapies (Simon et al., 2022).

Mohammed and Hawar examined the anticancer efficacy of biosynthesized silver nanoparticles derived from Moringa oleifera leaf extract. The cytotoxicity test results indicated that the AgNPs exhibited significant activity against the proliferation of the A375 cell line in comparison to WRL68 normal cells. Varying doses of AgNPs assessed the cell viability rate, demonstrating the capacity of AgNPs to inhibit cancer cell proliferation in a dose-dependent manner. The nanoparticles exhibited minimal efficacy against the A375 cell line at concentrations of 12.5 and 25 μg/mL, yielding effectiveness rates of 73.23% and 62.58%, respectively, with an IC₅₀ of 31.65 (Mohammed and Hawar, 2022).

Despite significant advancements in leukemia therapy and successful chemotherapy outcomes, patient survival remains limited, making access to viable alternative treatments for this malignancy essential. Global efforts are now underway to develop new technologies that can successfully eliminate tumors without seriously harming healthy cells, thereby overcoming the fundamental drawbacks of chemotherapy (Short et al., 2020). Accordingly, nanotechnology has emerged as one of the most promising cancer treatment solutions over the past 10 years. Metal nanoparticles in cell cultures and human tissues result in elevated levels of inflammatory products, including cytokines, and heightened oxidative stress, ultimately culminating in cell death. Nanoparticles are typically assimilated by the nucleus and mitochondria, resulting in DNA alterations, mitochondrial structural damage, and potential cell death (Jurj et al., 2017; Liu et al., 2020). Green nanoparticle production, characterization, and applications have recently emerged as major players in the subfield of nanotechnology. Xie et al. explored the green production of AgNPs using an aqueous extract of Nyctanthes arbortristis. In its current form, this synthetic approach is easy to use, inexpensive, and reproducible. To evaluate the formation of silver nanoparticles (AgNPs), various techniques such as X-ray diffraction, DLC, SEM, and UV-visible spectroscopy were utilized. The phytochemicals primarily responsible for nanotransformation were flavonoids, phenols, and glycosides found in the leaves. The in vitro cytotoxicity of AgNPs was assessed against human leukemia THP-1 cells at varying doses (5–50 μg/mL). Cell viability was reduced in THP-1 cells treated with AgNPs at concentrations ranging from 5 to 50 μg/mL. The findings indicates that the half maximum inhibitory concentration (IC₅₀) is 33.5 μg/mL (Kumari et al., 2018).

The application of plant-mediated synthesized AgNPs as prospective anticancer drugs is promising; however, numerous hurdles and future considerations must be addressed. Prior to human testing, AgNPs must be thoroughly evaluated for their toxicity, biocompatibility, and adverse effects (Stensberg et al., 2011; Levard et al., 2012). Over the past 10 years, a number of researchers have experimentally demonstrated that AgNPs are harmless in vitro, which differs greatly from in vivo settings (Hadrup et al., 2018; Upputuri and Pramanik, 2020). The toxicological properties of AgNPs are significantly influenced by parameters such as their size, morphology, surface curvature, and concentration (Ferdous and Nemmar, 2020). Important investigations have shown that silver and other nanoparticles are both acutely and chronically harmful in vivo (Cunningham et al., 2021). Although there is a widespread perception of the safety of medicinal plants and their extracts, it is crucial to recognize the presence of harmful medicinal plants when not administered at the appropriate dosage (Mugale et al., 2024). Therefore, extensive toxicity studies are essential to assess the safety of nanoparticles generated from medicinal plants for therapeutic applications. Although numerous studies have examined the efficacy of nanoparticles manufactured from medicinal plants, there has been comparatively little emphasis on their selectivity and safety in non-target cells. Long-term toxicity studies are essential to understand the cumulative effects of extended exposure, examine potential chronic toxicity, and evaluate the persistence of nanoparticles in the body over time (Ovais et al., 2016).

A further concern is the assurance of biocompatibility of the green-synthesized AgNPs. Although these nanoparticles demonstrate medicinal properties, their relationship with biological systems must be thoroughly studied to prevent toxicity or adverse reactions. The precise and effective administration of nanoparticles to designated cells or tissues continues to pose a problem. Formulating methods to precisely target cancer cells while reducing off-target effects is essential for efficient cancer treatment. AgNPs may aggregate or become unstable under physiological conditions. Maintaining stability and minimizing undesirable aggregation during preservation and administration are crucial for ensuring effectiveness. Optimization of the therapeutic application of NPs requires a comprehensive understanding of their pharmacokinetics and biodistribution. Their effectiveness and dispersion inside the body are influenced by various factors, including size, surface characteristics, and clearance mechanisms (Asam Raza et al., 2023). Furthermore, a number of additional recent studies have shown that nanoparticles are gradually excreted in urine and feces; nevertheless, the precise mechanism and important metabolic pathways involved remain unclear and require further investigation. The prolonged accumulation of nanoparticles in essential organs might result in significant toxicity; therefore, biodegradability and clearance concerns must be resolved by comprehensive mechanistic investigations prior to initiating clinical trials (Ovais et al., 2016; Drobne et al., 2018).