Research Article

Synthesis and Characterization of Biogenic Magnesium Oxide Nanoparticles as Anticancer Agent

Hassan Alauddin¹, Muhammad Arbaz Khan¹, Muhammad Aetesam Nasir¹, Nimra Jabeen¹, Fatima Fawad Janjua² and Muhammad Waqar Mazhar³

¹Department of Medicine and Surgery, Hitec-Institite of Medical Sciences, Taxilla cantt, Pakistan

²Department of Medicine and Surgery, Foundation University Medical college Islamabad, Pakistan

³Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan

Submission: July 02, 2024; Published: July 26, 2024

*Corresponding Address: Muhammad Waqar Mazhar, Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Pakistan, Email: waqarmazhar63@gmail.com

How to cite this article: Muhammad Waqar M. Synthesis and Characterization of Biogenic Magnesium Oxide Nanoparticles as Anticancer Agent. Canc Therapy & Oncol Int J. 2024; 27(2): 556209. DOI:10.19080/CTOIJ.2024.27.556209

Abstract

Suppressing the activity of enzymes that break down carbohydrates has proven to be an effective strategy for managing diabetes. Several inorganic compounds have been extensively examined to assess their potential as enzyme inhibitors. This study involved the synthesis of biogenic magnesium oxide nanoparticles (MgO NPs) utilizing Saccharomyces cerevisiae by reducing magnesium nitrate hexahydrate (Mg (NO3)2. 6H2O) salt solution. The present work showcased the anti-cancer properties of MgO NPs in laboratory conditions by assessing their efficacy in suppressing hepatocellular carcinoma cell lines (HepG2). The biologically produced MgO NPs were evaluated using UV Visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), and scanning electron microscope (SEM) with EDS profile.

The average size of MgO NPs synthesized using a green method was determined to be 24 nm. The results of molecular docking analysis indicate that MgO nanoparticles have a robust affinity towards the polar amino acids SER 30, ASP 37, and LYS 39 of α-glucosidase. The highest level of effectiveness of biogenic MgO nanoparticles was observed at a concentration of 100 μg/ml, and they were shown to be the most powerful inhibitor, reducing enzyme activity by 60%. Various doses of MgO nanoparticles, including 25 μg/ml, 50 μg/ml, and 100 μg/ml, were employed to suppress the growth of cancer cell lines. However, the highest concentration demonstrated the most significant inhibition. The efficacy of MgO NPs was also evaluated on retinal pigment epithelial cell lines (RPE) to determine its impact on normal cells. The findings revealed that MgO NPs specifically influence target areas without harming healthy cells.

Keywords: Nanotechnology; Biogenic synthesis; MgO NPs; Cytotoxicity; Anti-Cancer

Abbreviations: MgO NPs: Magnesium Oxide Nanoparticles; Mg (NO3)2. 6H2O: Magnesium Nitrate Hexahydrate; FTIR: Fourier Transform Infrared Spectroscopy; SEM: Scanning Electron Microscope; RPE: Retinal Pigment Epithelial Cell lines; IARC: International Agency for Research on Cancer; LMICs: Low- and Middle-Income Countries (LMICs); GCUF: Government College University Faisalabad; XRD: X-Ray Diffraction; FBS: Fetal Bovine Serum; DMEM: Dulbecco’s Modified Eagle’s Medium; PBS: Phosphate Buffer Saline; DMSO: Dimethyl Sulphoxide; EDS: Energy Dispersive Spectrum

Introduction

Worldwide, cancer ranks as the third leading cause of mortality. The International Agency for Research on Cancer (IARC) reports that about 9.6 million individuals lost their lives to cancer in 2018. As things stand, experts predict that there will be 17 million cancer deaths and 26 million new instances of cancer annually by 2030. As populations in low- and middle-income countries (LMICs) continue to expand, cancer risk factors like sedentary lifestyles, smoking, and irregular menstrual cycles are likely to become more common. You can avoid cancer by making changes to your lifestyle. Mutations in genes caused by environmental factors account for about 90-95% of cancer cases. Cancer has numerous potential causes, some of which can be avoided. Age, autoimmune illnesses, and genetics are not preventable causes of liver and cervical cancer, but avoidable risk factors include alcohol and tobacco use, obesity, infections, radiation, hepatitis B and C, and some HPV.

The α-glucosidase can be inhibited (antidiabetic activity) and malignant cells can be killed (cytotoxic activity) by nanoparticles. The size of nanoparticles ranges from 1 to 100 nanometers, and they are composed of various metals. There are a variety of methods for creating NPs, including physical, chemical, and biological ones. Both physical and chemical approaches have their drawbacks, such as the tremendous intensity needed to achieve the high temperatures and pressures needed to synthesize NPs and the release of harmful by-products into the environment.

This research aims to examine the antidiabetic and anticancer effects of yeast Saccharomyces cerevisiae by simulating the formation of MgO nanoparticles. Among the many microbes capable of extracellularly synthesizing Ag-NPs, ZnO Nps, and MgO NPs, the most notable include Cladosporium cladospo-rioides, Aspergillus clavatus, Fusarium oxysporum, Aspergillus fumigatus, Bacillus licheniformis, Fuserium semitectum, Penicillium brevicompactum, Klebsiella pneumoniae, and Aspergillus fumigatus. No one has ever shown the biogenic synthesis of MgO NPs from S. cervisiae extracellular extract. Consequently, this new research looks into how to efficiently make MgO NPs using an extracellular extract from S. cerevisiae.

Nanoparticles are used in various fields of life. Nanomaterials hold immense promise for significantly improving existing diagnosis, therapy, and designing novel approaches to treat a variety of human ailments. Nanotechnology may be able to create many new materials and devices, with a vast range of applications, such as in medicines, electronics, biomaterials, and energy production as shown in (Figure 1).

f1

Throughout the years, development in both polymer and nanoparticles chemistry has made it possible to synthesis and conjugation of functionalities that can react to stimuli. This is a significant advancement in cancer treatment since it allows for not only a passive targeting strategy but also passive targeting using carrier monoclonal antibody conjugates that can be triggered at any time.

Treatments based on nanotechnology, such as the creation of nanoscale medication delivery, can enable accurate cancerous tissue targeting while minimizing adverse effects. Nanoparticles can easily overcome cell barriers due to their biological composition. These nanostructures have been employed in the treatment of cancerous cells for many years due to their active and passive targeting capabilities [1]. Although numerous treatments can be used to treat tumors, their sensitivity often results in insufficient outcomes and can cause a variety of adverse effects, including damage to normal cells [2].

MgO nanoparticles synthesized from yeast Saccharomyces cerevisiae having the ability to kill the cancerous cells with a significant reduction in toxicity to normal cells. Nanomaterials are also being studied for their potential applications in intracellular delivery of DNA, RNAi, proteins, peptides, and tiny medicines to induce cancer cell death, as contrast agents for cancer imaging, and platforms for targeted gene and chemotherapeutics delivery to tumor locations [3].

Microbes based products have bioactive components which have anti-diabetic and tumor inhibitory properties [4]. Microorganisms have chemo preventive and chemotherapeutic compounds that have more than one mode of action to suppress oncogenes [5]. These extracts when used for the formation of nanoparticles will enhance the suppression of oncogenes and will be readily available and inexpensive [6]. Similarly, the targeted delivery of these chemicals to cancerous cells is another goal [7]. Nanoparticle synthesis from microorganisms is used to treat and cure cancer as they target cancerous cells only [8].

[9] demonstrated that silver nanoparticles have a significant effect on human cancer cell lines in MTT assay, although no cytotoxicity effect on normal cell lines. The biological synthesis of AgNPs with antibacterial and anticancer activity will help in the development of a symbiotic relationship between medical science and nanoscience to more effectively control deadly diseases [10]. Another study reported that The MgO nanoparticles synthesized from Lactobacillus sp. inhibit the growth of human leukemia cell lines HL-60, elucidating the potential of MgO nanoparticles for the therapy of leukemia.

Methodology

The current research work was designed to find out the formation of biogenic nanoparticles by using yeast Saccharomyces cerevisiae and characterization of their biological activities. This research work was conducted at Health Biotechnology Lab. Department of Bioinformatics and Biotechnology, Government College University Faisalabad (GCUF), Pakistan. The aim of this research project was to evaluate the enhanced activity of yeast after the formation of magnesium oxide nanoparticles as compared to simple bioactive components of other microbes.

Source and Purification of Yeast Strain

Saccharomyces cerevisiae S288-C is a pre-characterized strain gifted from Industrial Lab, Department of Bioinformatics and Biotechnology, Government College University, Faisalabad. The strain was already found to be an efficient production of various nanoparticles. The glycerol stock of S288-C was collected from -80 °C. Strain was cultivated on YEPD plates and the growth in yeast plates appears after 48 hours, thus it can be utilized for further purposes.

Extracellular biosynthesis of MgO NPs through Saccharomyces cerevisiae

Particularly magnesium resistant Saccharomyces cerevisiae strain (S288-C) was selected for the biosynthesis of MgO NPs.S. cerevisiae pure culture was inoculated into YEPD (yeast extract peptone dextrose) broth and shaken at 30 °C for 48 hours. After growth, the yeast biomass was separated using Whatman Grade 1 filter paper to get the cell-free filtrate. The resulting solution was centrifuged (HERMLE Labortechnik, Germany) at 5000 RPM for 20 minutes before being utilized in the biosynthesis of MgO NPs.

Under dark conditions, different concentrations of magnesium nitrate hexahydrate (as a precursor) were introduced drop wise to cell-free filtrate and incubated for 24 hours by shaking at 30 °C. The solutions were then allowed to stay at room temperature for 24 h. Finally, white sediment containing NPs was centrifuged at 4000 RPM for 30 minutes, washed three times with deionized water, then ethanol, and dried in a lyophilizer for 2 hours and store the sample for further purposes.

Characterization of magnesium oxide nanoparticles (MgO NPs)

UV-Vis Spectroscopy

The most common method for determining the optical characteristics and molecular structure of nanoparticles is spectroscopy. UV–Vis spectroscopy was used to confirm the produced MgO NPs in this study. The synthesis of MgO NPs using the Saccharomyces cerevisiae was monitored after the formation of white precipitates, using UV-Visible (UH5300, Hitachi Japan), in a wavelength range from 200 to 700 nm [11]. The powdered form nanoparticles were suspended in 1 ml of deionized water and then subjected to the spectrophotometer for UV-Vis analysis.

Fourier transform infrared spectroscopy (FTIR)

The potential biomolecules responsible for the reduction and capping of MgO NPs were identified using Fourier transform infrared spectroscopy (FTIR). FTIR analyzed the functional groups in nanomaterials by IR TRACER 100 in the range of 500-4000 cm^-1. The FTIR analysis was carried out on the dried powder of the MgO NPs and FTIR spectra was recorded [12]. The FTIR spectra clearly shows the well-known relationship of MgO nanoparticles optical characteristics on nanoparticle dimensions, such as the extinction cross-section, resonance wavelength, and scattering to absorption ratio.

X-ray diffraction (XRD) Analysis

The crystalline nature of the biogenic MgO NPs was examined through the XRD analysis as mentioned by (Ogunyemi et al., 2019). For the diffraction pattern analysis, a single drop of suspension of MgO NPs was coated over the surface of the glass substrate. X-ray diffractometer adjusted and the sample was placed at a voltage of 45 kV and 40 mA current with Cu Kα rays. At 0.04 step size and the 0.5 step time, the MgO NPs were scanned 2θ ranged from 10o-80o. The Cu Kα radiation wavelength was adjusted at 1.540 Å. The crystalline structure was manually examined, and the particle’s average size was found by using Debye-Scherrer’s formula given below

Where, D= crystal size (nm),

K is the Sharrer’s constant (0.9),

λ is the wavelength of X-rays source,

β is reflection peaks (radians) of full width at half maximum and

θ is peaks (radians) position.

SEM (Scanning Electron Microscopy) and EDS (Energy Dispersive X-ray) Analysis

The surface morphology and shape of biogenic MgO NPs was determined by using Field Emission Scanning Microscopy (Hitachi, Japan), which employed a novel field emission (CFE) gun for analytical performance and improved imaging quality. The SEM analysis was carried out according to the method described previously.

MTT Assay (Anti-Cancer Activity)

For MTT assay, Hep-G2 cells were plated in 96 well cell culture plates at a density of 2 × 104 cells per well. The plate was incubated at 37o C and 5% CO₂ for 24 hours in CO₂ incubator. 3 μl of MgO NPs were tested on cells. MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) solution of 10 μl was added in each well after 48 hours of incubation and plates were incubated for another 4 hours. 150 μl of DMSO (dimethyl sulphoxide) was added and optical density was measured at 490 nm. Statistical analysis was carried out using MS excel 2007 and graph pad prism 8 [13].

Where, A_c = absorbance of blank (negative control), and A_s= absorbance of sample (MgO NPs).

Cytotoxic Assay

The normal Retinal Pigment Epithelium (RPE) cell line was incubated at 37 °C in a temperature-controlled enclosed system 5% CO₂ in Dulbecco’s modified Eagle’s medium (DMEM) with gulta MAX enriched with 10% fetal bovine serum (FBS). To investigate the possible cytotoxic effects, cells were seeded at a concentration of 1 × 10⁵ cells per well in a 96-well culture plate and incubated under the conditions mentioned above. The cells were subjected to three different MgO NPs concentrations (25, 50 and 100 μg/mL) and a volume of 3 μl by keeping the phosphate buffer saline (PBS) as control with the same volume. After treatment, the plates were then incubated for 48h to perform the MTT assay. After the incubation period the MTT solution (10 μl) was added to each well and the plate is allowed to incubate again for 4h. The crystals of purple-colored formed were mixed in 150 μl of dimethyl sulphoxide (DMSO) solution. At a wavelength of 490 nm, the optical density was measured with a multi-well ELISA plate reader.

Results

Extracellular biosynthesis of MgO nanoparticles

The results shown in (Figure 2), confirmed that isolated yeast strain (S288-C) is able to synthesize the MgO NPs at 0.1 M concentration of Mg (NO₃)₂.6H₂O, yeast strain showed white precipitate deposited at the bottom of flask indicating the synthesis of MgO NPs.

Characterization of MgO NPs

UV-Vis Spectrophotometer Analysis of MgO NPs

The cultures of Saccharomyces cerevisiae S288C strain was incubated in a shaking incubator at optimum conditions (i.e. 28°C ±2 for 24 h) after the addition of 0.1 M Mg (NO₃)₂ solution independently. After incubation, white color precipitates at the bottom of the flask were observed which indicated the biosynthesis of MgO NPs. 3 ml of solution placed in a cuvette and subjected to UV-Vis spectrophotometry for the confirmation of MgO NPs. Then, centrifuged the sample present in the flask, discarded the supernatant and dry the pellet in a lyophilizer. After lyophilization, the solution of powdered from (which was in a purified form) NPs into ethanol was subjected to UV-Vis spectrophotometry again independently. One peak in the UV region was observed. The S288-C showed peaks at 270 nm. The peak in the UV-Vis spectrophotometer was used to confirm the biosynthesis of MgO NPs as shown in (Figure 3).

Scanning Electron Microscopy (SEM) analysis of MgO NPs

SEM images provide the surface morphology and size details of biogenic MgO NPs synthesized from potential yeast strainS288-C. The size of biogenic MgO NPs particles was measured with imageJ software from the SEM micrograph. SEM images at different magnitude scales ranging from 200X to 25,000X were collected and studied. The results of each MgO NPs sample showed variable morphological forms most of MgO NPs are present in spherical forms within average particle size ranging from (20-40 nm). Moreover, agglomeration was found between particles of larger sizes. SEM images of biogenic MgO NPs prepared from yeast strain Saccharomyces cerevisiae S288-C have shown in (Figure 4).

Fourier-Transform Infrared Spectroscopy (FTIR)

The FTIR analysis was used to investigate the explanation of functional groups involved in the tracellular biosynthesis of MgO NPs from yeast strain S288-C. This is the strongest technique for the investigation of the structural compounds. The analysis was carried out in the wave number ranging from 500-4000 cm^-1. The FTIR spectral of MgO NPs synthesized from S288-C shown in (Figure 5), showed prominent absorption peaks at 3699.96, 3423.06, 2932.76, 1652.16, 1538.04, 1413.78, 1129.18, 873.23, 557.26, 452.89, and 401 cm^-1. The strongest peaks at 3699.96 cm^-1 , 3423.06 cm^-1 and , 2932.76 cm^-1 , were observed due to the broad absorption of hydroxyl group (OH-) of alcohol and aldehydic C-H stretching, respectively (Moorthy et al. 2015). The peaks at 1652.16 cm^-1 and 1538.04 cm^-1, and were observed due to the stretching of O=C=O and a C=C stretching group of alkene, respectively. The peaks at 1413.78 cm^-1 and 1129.18 cm^-1 were due to the O-H group bonding and C-N group of amine stretching. The peaks at 557.26, 452.89, and 401 cm^-1 confirmed the presence stabilized MgO NPs with protein and alcoholic groups (Figure 5). FTIR spectrum confirmed the presence of active functional groups in Saccharomyces cerevisiae.

Energy Dispersive Spectrum Analysis (EDS)

The presence of elemental magnesium and oxygen was further confirmed by energy dispersive spectrum analysis (EDS). The EDS analysis of MgO NPs only showed the peak of magnesium and oxygen elements which confirmed the synthesis of NPs as showed (Figure 6), it is essential for NPs synthesis that there must not be any impurities and trace element amount observe. The analysis indicated the presence of magnesium content at the level of 54.61 %, oxygen content at the level of 40.98 %, and carbon content at the level of 4.42 % (Figure 6).

X-Ray Diffraction Analysis

The X-rays diffraction pattern of biogenic MgO NPs using Saccharomyces cerevisiae strain S288-C is depicted in (Figure 7). The analysis revealed that synthesis of MgO NPs was pure and crystalline in nature. The analysis results showed peak position of 2^θ ranging from 10^θ to 80^θ , at 23.86^θ , 19.16 ^θ , 35.63 ^θ , 52.74^θ , and 61.69^θ degree were assigned to the (111), (200), (220), (311), and (222) which were according to the data of standard diffraction value of MgO NPs (JCPDS card # 89-7746) indicating the crystalline nature of nanoparticles using the Debye–Scherrer equation.

MTT Assay (Anti-cancer activity)

Cytotoxic potential of the synthesized magnesium oxide nanoparticles against the hepatocellular carcinoma cell lines (HEPG-2) was evaluated by using MTT cytotoxicity assay. The synthesized MgO NPs showed a significant (p < .001) cytotoxic activity against the hepatocellular carcinoma cell lines. When the cells were treated with synthesized MgO NPs, the viability of the cells was constantly decreased in time and Figure. The cytotoxicity level of these MgO NPs against the hepatocellular carcinoma cell lines (HepG-2) at the different dose. These synthesized MgO NPs showed apoptotic properties at the doses of 25, 50, and 100 μg/ ml (Figure 8). He result demonstrated that, the sample showed inhibition 40.8277 % at the concentration of 25 μg mL^-1, while at the concentration of 50 μg mL^-1 represent 54.014 %, and maximum inhibition at 100 μg mL^-1 is 69.8918 % (Figure 9).

Cytotoxicity of MgO NPs

The cytotoxic effect of MgO nanoparticles is evaluated against the Retinal pigment epithelium (RPE) cell lines. The graph explains the cell viability percentage with MgO nanoparticles incorporation. At the three different nanoparticles concentrations (25, 50 and 100 μg/ ml), up to 95% cell survival rate was observed. Initially at 25 μg/ ml concentration of MgO NPs, the 94% of the cells were survived. The same percentage of cell viability was examined at 25 μg/ ml concentration. While at 100 μg/ ml concentration, the cell viability observed was 89 % (Figure 10). The cell viability data indicates that at lower concentration there is maximum cell viability, moreover, at higher concentration, a minor cell death was observed. It concludes MgO nanoparticles ensure the safety of normal cells, along with inhibition of the (α- glucosidase) enzyme (Figure 11).

Discussion

Nanoparticles can be synthesized either through biological or chemical methods. The biological methods are cheap, reliable, environmental friendly and easy, so they are gaining attention for the synthesis of nanoparticles and their beneficial role for mankind [14]. The biological interaction mainly depends on the crystallinity, shape and size of the nanoparticles. On the other hand, the size and crystallinity of nanoparticles changed with calcination temperatures (Nadaroglu, 2017) #29 reported the synthesis of nanoparticles done by using biological organisms such as bacteria, actinobacteria, yeasts, molds, algae, and plants, or other products. Molecules in plants, and microbes, such as proteins, amines, enzymes, phenolic compounds, alkaloids, and pigments perform nanoparticles synthesis by reduction.

In this research, the industrial yeast Saccharomyces cerevisiae was used to synthesize the monodispersed and more stable MgO NPs. Although the production of MgO NPs from fungal strain Aspergillus niger have previously been reported, the biogenic synthesis from yeast strain Saccharomyces cerevisiae has not been documented yet. There are several other associated advantages has been observed in different functional groups conjugated with the surface of MgO NPs making it suitable for various biomedical applications {Ammulu, 2021 #31} [15]. In the present study, UV-spectrophotometer was used to examine the synthesis of MgO nanoparticles produced from Saccharomyces cerevisiae; this demonstrated a characteristic peak for MgO NPs at 270 nm, confirming the formation of uniform and spherical MgO nanoparticles. [16] reported the synthesis of MgO NPs from Artemisia abrotanum herbal extract and UV-analysis of MgO NPs showed a sharp peak at 300 nm. A similar study [17] demonstrated the synthesis of MgO NPs and the UV absorption at 267 nm. Additionally, the crystallinity and stability of these NPs were confirmed by [18]. SEM results represent that some MgO nanoparticles are found in cluster form, which is supposed to be agglomerated, and some exist independently. The XRD pattern verified that MgO nanoparticles having a variety of phases including cubic, spherical and face-centered cubic. The crystal size of MgO NPs can be determined by using Debye–Scherrer’s formula [19].

The FTIR revealed active functional groups of MgO NPs by showing different peaks at different wavelength 3699.96, 3423.06, 2932.76, 1652.16, 1538.04, 1413.78, 1129.18, 873.23, 557.26, 452.89, and 401 cm^-1. Another study reported the FTIR spectra of MgO NPs including the peaks at 3433 , 2372, 2084, and 2079 , 1635 and 1632 cm^-1 [15].

Numerous studies have used MgO NPs to induce apoptosis in tumor cell lines [20]. Moreover, many studies have claimed the anti-bacterial, and anti-diabetic and anti-fungal properties of MgO NPs [15,21,22].The current research demonstrated that the anti-cancer and anti-diabetic activity of MgO NPs, which was synthesized from the yeast Saccharomyces cerevisiae.

Different concentrations of MgO nanoparticles were used against α-glucosidase including 25 μg /mL, 50 μg /mL and 100 μg /mL, but the maximum percentage inhibition was obtained at 100 μg /mL. MgO NPs showed less or no toxicity against normal cell lines (Retinal pigment epithelial cell lines) at the same concentration i.e. 25 μg /mL, 50 μg /mL and 100 μg /mL, and resulted in more than 80 % cell viability on these concentrations. Similar activity was reported by [23], using Ag NPs of different concentrations 50, 100, and 150 μg/ml. Another study by [24], reported Ag NPs inhibited α-glucosidase at 20-100 μg/ml. A study and investigated the synthesis of MgO from a different source (Pterocarpus marsupium rox.b) and determined the anti-diabetic activity but used a high concentration of MgO NPs nanoparticles (1-5 mg).

Despite the widespread use of MgO NPs, there are only a few studies to determine the cytotoxic effects of biologically synthesized MgO NPs, particularly in the context of apoptosis. MTT assay was used to appraise the effect of MgO NPs on the proliferation of hepatocellular carcinoma ell lines (HepG2) and retinal pigment epithelial normal cell lines. This is the first study to evaluate Saccharomyces cerevisiae-based MgO NPs against cancer cell lines. In the present study, biologically synthesized MgO NPs used at different concentrations such as 25 μg /mL, 50 μg /mL and 100 μg /mL, but more than 100 μg /mL had the potential to inhibit the cancerous growth. However, with a nanoparticle concentration of 100 μg /mL, the cell viability of the normal cell line (retinal pigment epithelial cell lines) was more than 90%, which represents that it could not inhibit other than target cells [25-41].

Summary

Nanotechnology has been innovated and used in the disciplines of biological science, materials science, environmental engineering, medicine, chemical, and other fields as a newly formed subject. Nanotechnology has been more significant in the diagnosis and treatment of diabetes in recent decades. Nanoparticles are a viable therapy option for cancer that has become resistant to traditional treatments. Nanoparticles with special designs deliver drugs like chemotherapy directly to tumors. They don’t give the medication out until they get to the target site. This prevents the medicines from harming healthy tissues in the tumor’s area.

References

1. Samadian H, Hosseini-Nami S, Kamrava SK, Ghaznavi H, Shakeri-Zadeh A (2016) Folate-conjugated gold nanoparticle as a new nanoplatform for targeted cancer therapy. J Cancer Res Clin Oncol 142(11): 2217-2229.
2. Hosseini M, Haji-Fatahaliha M, Jadidi-Niaragh F, Majidi J, Yousefi M (2016) The use of nanoparticles as a promising therapeutic approach in cancer immunotherapy. Artif Cells Nanomed Biotechnol 44(4): 1051-1061.
3. Senapati S, Mahanta AK, Kumar S, Maiti P (2018) Controlled drug delivery vehicles for cancer treatment and their performance. Signal Transduct Targeted Therap 3(1): 1-19.
4. Popli D, Anil V, Subramanyam AB, Rao SN, Govindappa M (2018) Endophyte fungi, Cladosporium species-mediated synthesis of silver nanoparticles possessing in vitro antioxidant, anti-diabetic and anti-Alzheimer activity. Artificial cells, Nanomed Biotechnol 46(Sup1): 676-683.
5. Nobili S, Lippi D, Witort E, Donnini M, Bausi L, et al. (2009) Natural compounds for cancer treatment and prevention. Pharmacol Res 59(6): 365-378.
6. Ovais M, Khalil AT, Ayaz M, Ahmad I, Nethi SK, et al. (2018) Biosynthesis of metal nanoparticles via microbial enzymes: a mechanistic approach. Int J Mol Sci 19(12): 4100.
7. Singh P, Kim YJ, Zhang D, Yang DC (2016) Biological synthesis of nanoparticles from plants and microorganisms. Trends Biotechnol 34(7): 588-599.
8. Singh P, Pandit S, Mokkapati V, Garg A, Ravikumar V, et al. (2018) Gold nanoparticles in diagnostics and therapeutics for human cancer. Int J Mol Sci 19(7): 1979.
9. Ahmed T, Shahid M, Noman M, Niazi MBK, Zubair M, et al. (2020) Bioprospecting a native silver-resistant Bacillus safensis strain for green synthesis and subsequent antibacterial and anticancer activities of silver nanoparticles. J Adv Res 24: 475-483.
10. Otari S, Patil R, Ghosh S, Thorat N, Pawar S (2015) Intracellular synthesis of silver nanoparticle by actinobacteria and its antimicrobial activity. Spectrochimica Acta Part A: Mol Biomol Spectrosc 136: 1175-1180.
11. Dobrucka RJIJ (2018) Synthesis of MgO nanoparticles using Artemisia abrotanum herba extract and their antioxidant and photocatalytic properties. Iran J Sci Technol Transact A: Sci 42(2): 547-555.
12. Ajaz S, Ahmed T, Shahid M, Noman M, Shah AA, et al. (2021) Bioinspired green synthesis of silver nanoparticles by using a native Bacillus sp. strain AW1-2: Characterization and antifungal activity against Colletotrichum falcatum Went. Enzyme Microb Technol 144: 109745.
13. Kim SO, Kim MR (2013) [6]-gingerol prevents disassembly of cell junctions and activities of MMPs in invasive human pancreas cancer cells through ERK/NF-κB/snail signal transduction pathway. Evid Based Complement Alternet Med 2013: 761852.
14. Gahlawat G, Choudhury AR (2019) A review on the biosynthesis of metal and metal salt nanoparticles by microbes. RSC Adv 9(23): 12944-12967.
15. Umaralikhan L, Jamal Mohamed Jaffar M (2018) Green synthesis of MgO nanoparticles and it antibacterial activity. Iranian J Sci Technol Transac A: Sci 42(2): 477-485.
16. Dobrucka R (2018) Synthesis of MgO nanoparticles using Artemisia abrotanum herba extract and their antioxidant and photocatalytic properties. Iran J Sci Technol Transact A: Sci 42(2): 547-555.
17. Vergheese M, Vishal SK (2018) Green synthesis of magnesium oxide nanoparticles using Trigonella foenum-graecum leaf extract and its antibacterial activity. J Pharmacogn Phytochem 7(3): 1193-1200.
18. Abinaya S, Kavitha H, Prakash M, Muthukrishnaraj A (2021) Green synthesis of magnesium oxide nanoparticles and its applications: a review. Sustain Chem Pharm 19: 100368.
19. Moorthy SK, Ashok C, Rao KV, Viswanathan C (2015) Synthesis and characterization of MgO nanoparticles by Neem leaves through green method. Materials Today: Proceedings 2(9): 4360-4368.
20. Karthik K, Dhanuskodi S, Kumar SP, Gobinath C, Sivaramakrishnan S (2017) Microwave assisted green synthesis of MgO nanorods and their antibacterial and anti-breast cancer activities. Material Lett 206: 217-220.
21. Sierra-FA, De La Rosa-GS, Gomez-Villalba LS, Gómez-Cornelio S, Rabanal ME, et al. (2017) Synthesis, photocatalytic, and antifungal properties of MgO, ZnO and Zn/Mg oxide nanoparticles for the protection of calcareous stone heritage. ACS Appl Mater Interf 9(29): 24873-24886.
22. Tan KX, Jeevanandam J, Pan S, Yon LS, Danquah MK (2020) Aptamer-navigated copolymeric drug carrier system for in vitro delivery of MgO nanoparticles as insulin resistance reversal drug candidate in Type 2 diabetes. J Drug Delivery Sci Technol 57: 101764.
23. Padalia H, Chanda S (2021) Synthesis of silver nanoparticles using Ziziphus nummularia leaf extract and evaluation of their antimicrobial, antioxidant, cytotoxic and genotoxic potential (4-in-1 system). Artificial Cells, Nanomed Biotechnol 49(1): 354-366.
24. Balan K, Qing W, Wang Y, Liu X, Palvannan T, et al. (2016) Antidiabetic activity of silver nanoparticles from green synthesis using Lonicera japonica leaf extract. RSC Adv 6(46): 40162-40168.
25. Adwas AA, Azab AE, Quwaydir FA (2019) Cancer: Insights into Epidemiology, Classification, Aetiology, Diagnosis, Prevention, and Cancer Chemotherapy.
26. Amina M, Al Musayeib NM, Alarfaj NA, El-Tohamy MF, Oraby HF, et al. (2020) Biogenic green synthesis of MgO nanoparticles using Saussurea costus biomasses for a comprehensive detection of their antimicrobial, cytotoxicity against MCF-7 breast cancer cells and photocatalysis potentials. PLoS One 15(8): e0237567.
27. Beaglehole R, Bonita R, Magnusson R (2011) Global cancer prevention: an important pathway to global health and development. Public Health 125(12): 821-831.
28. Chauhan A, Zubair S, Tufail S, Sherwani A, Sajid M, et al. (2011) Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer. Int J Nanomed 6: 2305-2319.
29. Ezhilarasi AA, Vijaya JJ, Kaviyarasu K, Maaza M, Ayeshamariam A, et al. (2016) Green synthesis of NiO nanoparticles using Moringa oleifera extract and their biomedical applications: Cytotoxicity effect of nanoparticles against HT-29 cancer cells. J Photochem Photobiology B: Biology 164: 352-360.
30. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JWW, et al. (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49(6): 1374-1403.
31. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5): 646-674.
32. Jabir MS, Hussien AA, Sulaiman GM, Yaseen NY, Dewir YH, et al. (2021) Green synthesis of silver nanoparticles from Eriobotrya japonica extract: a promising approach against cancer cells proliferation, inflammation, allergic disorders and phagocytosis induction. Artif Cell Nanomed Biotechnol 49(1): 48-60.
33. Khashan KS, Sulaiman GM, Hussain SA, Marzoog TR, Jabir MS (2020) Synthesis, characterization and evaluation of anti-bacterial, anti-parasitic and anti-cancer activities of aluminum-doped zinc oxide nanoparticles. J Inorg Organomet Polym Mater 30(9): 3677-3693.
34. Küünal S, Rauwel P, Rauwel E (2018) Plant extract mediated synthesis of nanoparticles Emerging applications of nanoparticles and architecture nanostructures. Elsevier pp. 411-446.
35. Mohanasrinivasan V, Subathra Devi C, Mehra A, Prakash S, Agarwal A, et al. (2018) Biosynthesis of MgO nanoparticles using Lactobacillus sp. and its activity against human leukemia cell lines HL-60. Bio Nano Science 8(1): 249-253.
36. Noor S, Shah Z, Javed A, Ali A, Hussain SB, et al. (2020) A fungal based synthesis method for copper nanoparticles with the determination of anticancer, antidiabetic and antibacterial activities. J Microbiol Methods 174: 105966.
37. Ramar M, Manikandan B, Marimuthu PN, Raman T, Mahalingam A, et al. (2015) Synthesis of silver nanoparticles using Solanum trilobatum fruits extract and its antibacterial, cytotoxic activity against human breast cancer cell line MCF 7. Spectrochimica Acta Part A: Mol Biomol Spectrosc 140: 223-228.
38. Thamer NA, Barakat NT (2019) Cytotoxic activity of green synthesis copper oxide nanoparticles using cordia myxa L. aqueous extract on some breast cancer cell lines. J Physics: Conference Series.
39. Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global Cancer Incidence and Mortality Rates and Trends-An Update Global Cancer Rates and Trends-An Update. Cancer Epidemiol Biomarkers & Prevention 25(1): 16-27.
40. Verma R, Gurmaita A (2019) A Review on anticarcinogenic activity of “Centella asiatica”. Endangered Species 6: 7.
41. Vijayakumar S, Vaseeharan B, Malaikozhundan B, Shobiya M (2016) Laurus nobilis leaf extract mediated green synthesis of ZnO nanoparticles: characterization and biomedical applications. Biomed Pharmacother 84: 1213-1222.