One of the latest and important classes of porous materials are metal-organic framework (MOF) nanostructures, with industrial importance in diverse fields. These classes of organic and inorganic frameworks composed of metallic or metal oxide structural units are bound together by organic molecules and form interconnected porous structures (Langseth et al., 2019).

It is important to exploit and commercialize MOF production methods that are sustainable, mass-produced, and cost-effective (Julien et al., 2017; Reinsch and Stock, 2017; Zhu et al., 2022). Therefore, green synthesis is possible to produce MOFs using non-toxic and efficient materials (Thornton et al., 2016; Taddei, 2017). One of the most important advantages of green synthesis is the non-use of toxic solvents such as dimethylformamide (DMF) and synthesis at ambient temperature and pressure, as well as lower activation temperatures to eliminate the byproducts and guest molecules in MOFs (Reinsch and Stock, 2017; Zhang et al., 2020a; Yang, 2021). Therefore, we need to use water for the green synthesis of MOFs because water is more accessible and vibrant than organic solvents. However, the important point here is that most of the water-soluble organic bonds are weak and cause the instability of MOFs (Gelfand and Shimizu, 2016; Shih et al., 2017). This method may hence not be suitable for mass production, but the time of MOFs synthesis involving metal ions bonding, and the natural organic framework is shorter and less significant than that in other methods. To date, the aqueous synthesis of MOFs using chemistry offers made major benefits. In these methods, the water-solubility issues have been mitigated mainly by using sodium salts of the organic linkers and by increasing the length of the tubing systems to increase the overall reaction time (Bayliss et al., 2014; Sánchez-Sánchez et al., 2015; Avci-Camur et al., 2018).

Therefore, we use Satureja hortensis extract of organic compounds, such as chlorogenic acid, caffeic acid (CA), gallic acid, ferulic acid, and \rho-cymene as the organic framework (Movahhedkhah et al., 2019) and used sodium salts for a faster and better reaction. Most of the ingredients in the extract of savory are CA, which converts to CA despite the presence of a large amount of organic matter in the extract (Milos, 2001). As mentioned, one of the polyphenols produced through the secondary metabolism of vegetables is CA (Espíndola et al., 2019).

CA participates in the defense mechanism of plants against predators, pests, and infections, as it has an inhibitory effect on the growth of insects, fungi, and bacteria (Tosovic, 2017) as well as promotes the protection of plant leaves against ultraviolet radiation B (UV-B) (Gould et al., 2000; Tosovic, 2017). In vitro and in vivo experiments have been performed and demonstrated innumerable physiological effects of CA and its derivatives, such as antibacterial (Verma and Hansch, 2004; Genaro-Mattos et al., 2015), anti-hepatocarcinoma (HCC) (Zhang et al., 2017), antioxidant (Lin and Yan, 2012; Huang et al., 2013; Genaro-Mattos et al., 2015), anti-inflammatory (Lin and Yan, 2012; Huang et al., 2013; Genaro-Mattos et al., 2015), anticancer (Lin and Yan, 2012; Huang et al., 2013), and anti-hepatocellular carcinoma activity (Gu et al., 2016). Among these properties, the anti-HCC activity is highlighted because HCC is one of the main causes of cancer mortality in the world (McGlynn et al., 2015). Therefore, further studies on the chemical and pharmacological aspects of CA are necessary to contribute to the future development of a new drug and, consequently, to the expansion of therapeutic possibilities (Zhang et al., 2017).

Aluminum (Al) is one of the most abundant metals with non-toxic salts that are easy to use and also economical. In addition, Al nanoparticles (Al-nano) may be a good choice for anticancer immunotherapy, which should possess good safety and efficacy. Al-nano such as aluminum hydroxide and phosphate or hydroxy phosphate aluminum have excellent safety properties for systemic vaccination. In fact, it has been used as an adjunct for over half a century and is now one of the most widely used adjuncts in animal and human vaccines (Lindblad, 2004; Mesa and Fernández, 2004). Muehlmann and Sun et al., for example, demonstrated that aluminum oxide nanoparticles as drug carriers are promising for photodynamic cancer therapy as well as for the activation of the immune system in cancer diseases (Lin and Yan, 2012). Wang et al. revealed the use of aluminum anode nanotubes as a carrier of anticancer drugs is shown on the MDA cancer cell line. Protein from the family of tumor necrosis factors that induce apoptosis was used as a model drug. Anodic alumina nanotubes that have been structurally engineered can be used as nano-carriers for the delivery of anticancer therapeutics (Hou et al., 2021). So, the oxidation of aluminum and copper has anticancer and antimicrobial properties due to its highly porous structure. Therefore, we have chosen one type of Al-MOFs as a carrier for the anti-proliferative herbal extract (Zeraati et al., 2021a). The Al-MOFs seem to be more effective against the proliferation of breast cancer cells when compared with herbal extraction. Therefore, Al-MOFs have received much attention (Senkovska et al., 2009; Moreno et al., 2018). A challenge in the investigation of Al-MOFs is the rich solution chemistry of Al³⁺, which gives rise to a variety of inorganic building units ranging from isolated Al³⁺ ions that are exclusively connected by the carboxylate groups to trimeric building units, rings of edge- and corner-sharing AlO₆ polyhedra, chains of trans- or cis-corner sharing AlO₆ polyhedra, chains of edge-sharing AlO₆ polyhedra, or flexible inorganic building units of corner-sharing Al₁₃-oxo clusters. Therefore, the study of Al-MOF can provide a new step toward cancer treatments.

As a result, the use of green sources as a link precursor can be regarded as a revolution in MOF preparation. Ionic liquids, natural oils, and plant extracts are examples of such sources, all of which have a high level of acceptability in terms of green technology (Liu et al., 2013; Zeraati et al., 2021a). Green MOF synthesis also reduces the need for organic solvents, operates at low temperatures and pressures, and requires less time to react. These benefits have increased the efficiency of the green technique (Zeraati et al., 2021b).

In this study, the green synthesis of Al-MOF was developed by using S. hortensis extract as an organic framework and NaOH as a salt linker. The products were characterized by Fourier-transformed infrared (FTIR) spectroscopy, field-emission scanning electron microscopy (SEM), transmission electron microscopy (TEM), and N₂ adsorption/desorption isotherm. The final Al-MOF products were investigated for their anticancer properties in detail. Figure 1 illustrates the flowchart of the study method.

The reagents used for the chemical synthesis of Al-MOF are aluminum nitrate [Al(NO₃)₃·9H₂O], deionized (DI) water (H₂O), and S. hortensis extract as the green organic linker. The S. hortensis extract was prepared by taking 10 g of dry Satureja cut (harvested from Gdboft in Kerman province of Iran) and immersing it in 100 ml of distilled boiled water for 5 min, followed by cooling and filtering through centrifugal spinning at 4,000 rpm thrice. The Markham method was used to extract flavonoids (Couderchet et al., 1997). Primarily, 250 ml of 2% AlCl₃.·6H₂O solution was mixed with 40 ml S. hortensis aqueous extract. After storage for 15 min at room temperature, the absorbance response was measured at 430 nm. This data was expressed as milligram per gram of dry matter. The synthesis process was performed in an ambient atmosphere. First, 3.3 g of Al precursor [Al(NO₃)₃·9H₂O] was dissolved in 12.5 ml of DI water as the solvent at 80°C. Then (S1) 12.5 ml of the Satureja extract was added to the Al solution, and (S2) 12.5 ml of S. hortensis extract and 1 ml of 50% NaOH solution were added to the Al solution with aggressive stirring at 300 rpm. In this step, the transparent colloidal of the initial solution changed in color to light yellow. The synthesis process was prolonged to 60 min until the formation of white precipitate from the yellow solution at the same temperature. The precipitate was then collected and dried. Finally, considering the results of the thermal analyses, the prepared sample was maintained at 120°C in a vacuum oven for 5 min to active its structure. Morphological and structural characteristics of the prepared samples were performed using the Nanosem 450. The field-emission SEM (FE-SEM) images were acquired with the Inspect F SEM (FEI) operating at 3 kV and equipped with an energy dispersive X-ray (EDX) spectroscopy and TEM. The FTIR spectra of the samples were measured on the Varian LS Chemical Imaging Microscope at 4,000–400 cm−1 and the Brunauer–Emmett–Teller (BET) model from the nitrogen adsorption/desorption isotherms of the samples were obtained using 196°C (77 K) after separation at 200°C and 10–5 mm Hg for at least 4 h. The surface-specific regions (SBETs) were calculated from the adsorption isotherm data using the BET method. The mesoporous size distribution and total mesoporous volume were determined using the modified Barrett–Joyner–Halenda (BJH) method of isotherm adsorption data. The human breast cancer (MDA-MB-468) cell line was provided from the Iranian Biological Resource Center (IBRC; Tehran, Iran). Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), phosphate-buffered saline (PBS), trypsin/EDTA solution, 3-(4,5-dimetylthiazol-2-Yl)–2,5–diphenyltetrazolium bromide (MTT), and dimethyl sulfoxide (DMSO) were purchased from Gibco BRL and Sigma, respectively. They were cultured in DMEM (Gibco, United Kingdom) supplemented with 10% FBS (Gibco) and 1% penicillin–streptomycin (Gibco) and incubated in a 5% CO2 atmosphere at 37°C. For treatment, 5 × 103 cells/well were seeded in 96-well flat-bottomed plates overnight, then the cells were exposed to various concentrations of the herbal extract (0–100 μM) and Ag-MOF (0–100 μM) for 24 and 48 h. Subsequently, the medium was removed, and 200 μL of MTT solution (5 mg/ml in PBS) was added to each well and incubated for 4 h at 37°C. After discarding the solution, 100 μL of DMSO was added and the plates were shaken for 15 min. The absorbance of each sample was read at 570 nm using an ELISA microplate reader. The outcomes were affirmed as a percent of cell viability with respect to the untreated control cells.

The novel Al-MOF was prepared by using S. hortensis extract as an organic framework with NaOH as a salt linker. The final products were characterized by relevant analyses. The main group was confirmed by FTIR spectroscopy. TEM exhibited the spherical morphology of the structure with porosity nature arranging the compound. The N2 adsorption/desorption isotherm of Al-MOF nanostructure was similar to the IV type-classical isotherms, which confirmed the significant porosity of Al-MOF nanostructures. The final Al-MOF sample was examined for anticancer treatment, and the results confirmed the remarkable activity of this novel compound. The present study can open a new window to the introduction of new anticancer materials. The nature of Al-MOF, the natural S. hortensis extract linker, and the purification procedure were explored in this work. The physico-chemical properties of the samples obtained in this study can be attributed to select novel nanostructure as well as an optimization process. The anticancer features obtained in this study can be opened a new window for developing new material.