Green Synthesis of Metal and Metal Oxide Nanoparticles Using Different Plants’ Parts for Antimicrobial Activity and Anticancer Activity: A Review Article

Nanotechnology emerged as a scientific innovation in the 21st century. Metallic nanoparticles (metal or metal oxide nanoparticles) have attained remarkable popularity due to their interesting biological, physical, chemical, magnetic, and optical properties. Metal-based nanoparticles can be prepared by utilizing different biological, physical, and chemical methods. The biological method is preferred as it provides a green, simple, facile, ecofriendly, rapid, and cost-effective route for the green synthesis of nanoparticles. Plants have complex phytochemical constituents such as carbohydrates, amino acids, phenolics, flavonoids, terpenoids, and proteins, which can behave as reducing and stabilizing agents. However, the mechanism of green synthesis by using plants is still highly debatable. In this report, we summarized basic principles or mechanisms of green synthesis especially for metal or metal oxide (i.e., ZnO, Au, Ag, and TiO2, Fe, Fe2O3, Cu, CuO, Co) nanoparticles. Finally, we explored the medical applications of plant-based nanoparticles in terms of antibacterial, antifungal, and anticancer activity.


Introduction
Technology and science are moving at the highest rate for developing green technology. Nanotechnology is one of the most interesting topics utilized to produce and employ materials having interatomic structural characteristics. Nanotechnology emerged as scientific innovation in the 21st century. Nanoparticles can be defined as particles having the size in the range of 1-100 nm and exhibited dimensions on a scale of one-billionth of a meter [1][2][3]. Nanoparticles are advanced materials in technology and science and have various applications in agriculture [4,5], medical [6], electronic [7], chemical [8], and pharmaceutical [9] fields. The biosynthesis of nanoparticles with desired morphology (shape, size, and crystalline nature) has been one of the basic aims in chemistry that can be utilized for various applications, e.g., catalysis, biomedical, lower-cost electrode, and biosensor [10][11][12]. Except for their unique chemical and physical properties, nanoparticles behaved as a bridge between molecular or atomic structure and bulk materials. Thus, they are the best candidate for many important applications such as biotechnology, trace substance identifications, medical, and electrochemistry [13][14][15][16]. Different synthetic approaches have been used for the fabrication of nanoparticles with desired the morphology

Green Chemistry and Sustainable Principle
Green chemistry for sustainable development has been reported for less than 15 years [21]. Sustainable development can be termed as the development that accounts for and includes the needs of presently fulfilling and the capability of incoming generations [22]. Sustainable development has unique importance for industrial chemistry because it is concerned with pollution and the use of natural sources [23]. Chemistry has been considered a toxic branch of science, and, normally, the word chemical is associated with toxicity and hazards [24]. Generally, there are many methods to reduce risk by using protection, which is known as protective gear. When these methods fail, the risk of toxicity and hazards is increased. Due to high toxicity and hazards, the outcome can be more harmful, like injuries and deaths [25,26]. Therefore, safe, sustainable methods and procedures help to decrease toxicity and hazard to reduce the danger of accidents and damages [27,28].

Synthesis of Metal and Metal Oxide Nanoparticles Using Plants
In biological synthesis (using different organisms such as plants, bacteria, fungi, algae, and actinomycetes) of metal or metal oxide nanoparticles, ecofriendly accepted "green chemistry" ideas have been employed [29]. Biological synthesis of nanoparticles via biological organisms is summarized as a green substitute for the synthesis of nanoparticles having desired properties. In biological synthesis, both types of organisms (i.e., unicellular and multicellular) are permitted to react [30]. Plants are well-known chemical factories of nature that are inexpensive and ecofriendly. Plants have shown remarkable potential in heavy metals' detoxification and collection, by which environmental contamination and pollutants' problems can be resolved because the traces of these heavy metals are also hazardous. There are many benefits for nanoparticles' synthesis via plant extract as compared to other biosyntheses such as by bacteria, fungi, actinomycetes, and algae [31]. One advantage of plant-mediated NPs is that the kinetics for this method are sufficiently higher than other biological methods. Different parts of plants, i.e., leaf, stem, seed, fruit, and roots, have been extensively used for the biosynthesis of nanoparticles because of the presence of remarkable phytochemicals [32]. For the synthesis of nanoparticles, specific parts of the plant are washed with tap or distilled water, after squeezing, filtering, and adding respective salt solutions, whose nanoparticles we wish to synthesize. The color of the solution begins to change, thus revealing the synthesis of nanoparticles, which we can separate easily.

Role of Capping Agents in the Synthesis of Metal and Metal Oxide Nanoparticles
Capping agents play an essential role in the synthesis of nanoparticles' formation. The main role of the capping agent is to stabilize and functionalize the nanoparticles. By using a capping agent, we can impart the useful or desired properties to nanoparticles by controlling size and protecting the surface area and morphology. Various surfactants have been used as a capping agent for changing the desired morphology of nanoparticles, but these surfactants are very tough to remove. Moreover, these surfactants are toxic to our ecosystems [33]. Due to these limitations, there is a need to use ecofriendly capping agents and develop a green route at a commercial and non-commercial level for nanoparticles' formation.

Role of Phytochemicals in the Synthesis of Metal and Metal Oxide Nanoparticles
The biosynthesis of nanoparticles compromises three main ingredients, e.g., solvent medium, reducing agents, and stabilizing agents [34][35][36]. To prepare plant-mediated nanoparticles, the photo component of plant extract serves as a reducing and stabilizing agent. Now, researchers have focused on plant-mediated nanoparticles' biosynthesis due to more advantages over conventional physical and chemical synthetic procedures [37][38][39][40][41][42][43][44].

Role of Amino Acid in Green Synthesis of Nanoparticles
Synthesis of nanoparticles using bio-molecules has recently attained much interest because of their non-hazardous nature and because they do not involve harsh methods. Amino acid serves as an excellent capping and reducing agent to prepare nanoparticles having a specific structure. Maruyama and coworkers prepared gold nanoparticles with a size range of 4-7 nm by amino acid as a capping agent. There are 20 different types of amino acids. Among these different types, they used L-histidine, which reduced tetraauric acid to gold nanoparticles. The concentration of amino acid (L-histidine) affects the size of nanoparticles. The size of nanoparticles is decreased with an increase in the concentration of amino acids [45]. Qing-Hua Xu reported a single-step formation of gold nanoparticles by using two amino acids (glutamic and histidine) [46]. Meghana Ramani synthesized ZnO nanoparticles of different shapes and sizes by using three types of amino acids such as l-glutamine, l-alanine, and l-threonine. These amino acids played an important role as a capping agent. The surface modification of ZnO nanoparticles due to a capping agent was confirmed by FTIR spectroscopy [47].

Role of Protein in Green Synthesis of Nanoparticles
In the biosynthesis of nanoparticles, the vital role of proteins cannot be ignored. Proteins can offer a vital role of reduction, by which they donate e (electron) to the Ag+ ion that leads to the synthesis of silver nanoparticles. Recent studies report the potential role of proteins in the formation of silver nanoparticles by using Capsicum annum [48]. The absorption spectra of UV-Vis (ultraviolet-visible spectroscopy) showed a strong absorption peak at 210 nm, which the authors attributed to the existence of a peptide bond. While the peak was around 280 nm, the UV-Vis absorption spectrum showed the existence of amino acids, e.g., phenylalanine and tyrosine, that tend to react with silver ion. In another study, casein was utilized as a stabilizing and reducing agent in the synthesis of silver nanoparticles [49]. For the confirmation of the role of protein in the process of formation of nanoparticles, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis of leaf extracts of Olax scandens and concentrated supernatants of O. scandens-based silver nanoparticles was performed. The results illustrated that some low-molecular-weight peptide bonds present in the extract of leaf were absent in the obtained nanoparticles. Such proteins of low-molecular-weight have been utilized in biosynthesis phenomena. NPs unite with proteins and form a dynamic nanoparticle-protein corona [50]. Similar results were studied in the soya been-mediated synthesis of gold nanoparticles [51].

Role of Carbohydrates or Saccharides in Green Synthesis of Nanoparticles
The recent study also showed the role of carbohydrates of saccharides in the synthesis of nanoparticles. Raveendran and coworkers utilized sugar and starch as nanoparticlesreducing or -stabilizing agents, respectively. In another study, glucose and hemicellulose were utilized for the synthesis of nanoparticles [52,53]. Polysaccharides are the major class of carbohydrates' molecules with repeating units of mono-and disaccharides that linked each other by a glycosidic bond. Polysaccharides served as a capping agent in the synthesis of nanoparticles. These are the advantages of polysaccharides as a reducing agent: The green synthesis is performed in the presence of water as a solvent, therefore removing the use of a toxic solvent [54,55]. One of the unique characteristics of polysaccharides is that they sharply accelerate the kinetics of sol-gel methods because of their catalytic effect [56]. Shu-Juan Bao reported an eco-friendly, bio-mimetic method for the synthesis of TiO 2 nanomaterials. Polysaccharides not only have been found to modify the size, shape, and structure of TiO 2 but have induced various phases; rutile phase has been achieved in the presence of chitosan and the anatase phase has been achieved in the presence of starch.
Dextran is a branched polysaccharide that consists of many glucose molecules with a chain of different lengths. Gold nanoparticles were synthesized using natural honey that served as a reducing agent. Fructose in the honey was considered to serve as a reducing agent, while proteins were responsible for the stabilization of nanoparticles [57]. Gold nanoparticles were synthesized using amino cellulose that acted as capping as well as reducing agents.

Role of Phenolics Acid in Green Synthesis of Nanoparticles
Phenolic acid is a very essential phytochemical that belongs to the polyphenols' family. It is composed of two important functional groups, i.e., carboxylic acid and phenolic ring. Various types of phenolic acid, i.e., ellagic acid, caffeic acid, protocatechuic acid, and gallic acid, are reported as reducing agents for the preparation of metal nanoparticles [58]. It is reported that silver nanoparticles can be prepared upon the formation of a transitional complex of Ag + with gallic acid. Consequently, through oxidation phenomena, it converts to quinine that forms silver nanoparticles [59,60].

Role of Flavonoid in Green Synthesis of Nanoparticles
Flavonoid is the component of plants' pigment that compromises a class of secondary metabolites because of their diversity and biological synthesis in plants [61]. Up until now, 7000 different flavonoid molecules have been reported. Flavonoids can be present in various forms, e.g., flavonol, isoflavones, anthocyanidins, flavones, flavanones, and flavan3-ol. Flavonoids are considered a basic bio-reducing agent of plant extract and their reducing ability is due to their ability to donate hydrogen ions or electrons [62]. Various articles have been published on the electron or hydrogen ion-releasing capability of flavonoids utilized for the preparation of nanoparticles [63][64][65]. Thus, flavonoids in an extract of the plant are currently utilized as a necessary tool for the primary assessment of untapped plants for the preparation of nanoparticles [66]. In another report, it was reported the production of free hydrogen ions during keto-enol conversion of flavonoids, e.g., rosmarinic acid and luteolin can be intended to reduce silver ions for the synthesis of silver nanoparticles [67]. In another report, it was reported hydrogen ions of flavonoids during the reduction of metal salt can oxidize to the carbonyl group [68]. In an extract of Ocimum basilicum, the transformation of enol-to keto-is a key factor in the biosynthesis of silver nanoparticles [69].

Role of Terpenoids in Green Synthesis of Nanoparticles
Terpenoids or isoprenoids are very important phytochemical that belongs to naturally synthesized terpenes. They are derivatives of essential oil, which are a mixture of secondary metabolites induced by plants. Previous studies have described the importance of these metabolites in the preparation of silver nanoparticles [70]. It was reported that two important terpenoids, e.g., sesquiterpenoids and monoterpenoids, are basic constituents for the silver nanoparticles' synthesis [71]. Various reports showed the importance of essential oil of different plants' species in the synthesis of silver nanoparticles such as Cocos nucifera [72], rosemary [73], Ricinus communis [74], and Anacardium occidentale [75].

Synthesis of Metal or Metal Oxides' Nanoparticles by Using Plants
In this review article, we summarized the basic principles or mechanisms of the green synthesis method, especially for metal or metal oxide (i.e., ZnO, Au, Ag, TiO 2 , Fe, Fe 2 O 3 , Cu, CuO, Co) nanoparticles.

Zinc Oxide Nanoparticles
Recently, Zinc oxide nanoparticles have emerged as one of the most significant metal oxide nanoparticles due to carrying specific differences in morphology (size, shape, and crystalline nature), applications, low toxicity, economic benefits, and bio-compatibility [76][77][78]. Zinc oxide nanoparticles can be prepared from various parts of a plant such as a leaf, Stem, root, flower, seed, and fruit. To date, numerous leaves' extracts have been used for the synthesis of ZnO nanoparticles, as shown in Table 1.
Piper betle aqueous leaf extract was applied for the synthesis of ZnO nanoparticles with an average size of 112 nm. S. aureus (ZOI = 2-3 mm) and E. coli (ZOI = 1-4 mm) are main causes of surgical site infection (SSI). Globally, SSI accounts for 2.5% to 41.9%, and an even higher rate in developing countries. Surgical site infection affects not only the health of patients but also the development of the country. The anti-bacterial agents are a significantly effective solution to lower this rate and Piper betle-mediated ZnO nanoparticles were proven to show excellent antibacterial activity against S. aureus and E. coli [82]. Becium grandiflorum was reported for the biosynthesis of ZnO nanoparticles and evaluated antimicrobial activity against S. aureus (ZOI = 7 mm), E. coli (ZOI = 6 mm), K. pneumonia (ZOI = 8 mm), and P. aeruginosa (ZOI = 11mm) bacteria, shown in Figure 3. Methyl blue dye from an aqueous solution was effectively removed by synthesized ZnO nanoparticles [83]. In another study, ZnO nanoparticles were prepared from aqueous leaf extract of Achyranthes aspera and evaluated for antibacterial activity against S. gallinarum and S. enteritidis using the agar wall diffusion method. The author also observed that Achyranthes aspera-mediated ZnO nanoparticles showed zone of inhibition (ZOI) of 31 mm against S. enteritidis and S. gallinarum showed 30 mm [84]. Spherical-shaped ZnO nanoparticles with a size range of 30-55 nm were fabricated using an aqueous leaf extract of Arthrospira platensis. The results showed that antimicrobial activities of Arthrospira platensis-mediated nanoparticles were dose-dependent. Their application as an anti-microbial agent was studied and formed clear zones of 24.1 ± 0.3, 21.1 ± 0.06, 19.1 ± 0.3, 19.9 ± 0.1, and 21.6 ± 0.6 mm, at 200 ppm against B. subtilis, S. aureus, P. aeruginosa, E. coli, and C. albicans, respectively. These antibacterial activities were reduced as synthesized ZnO concentration decreased. ZnO nanoparticles showed significantly higher cytotoxic efficacy against cancerous cells than normal cell lines [85]. Hexagonal-shaped ZnO nanoparticles with a crystallite size of 17 nm were produced from ethanol leaf extract of Sambucus ebulus. The synthesized ZnO nanoparticles showed acceptable photo-catalytic degradation of Methylene blue dye. Sambucus ebulus-mediated ZnO nanoparticles explain efficient antioxidant and antibacterial activity [86]. Droepenu, Eric Kwabena, et al. reported the biosynthesis of ZnO nanoparticles using Anacardium occidentale and tested against S. aureus (ZOI = 1.06 ± 0.14 mm), E. aquaticum (ZOI = 1.99 ± 0.11 mm), K. pneumoniae (ZOI = 2.08 ± 0.03 mm), E. coli (ZOI = 1.49 ± 0.09 mm), and A. baumanii (ZOI = 2.99 ± 0.01 mm) [87].
From 2020 to 2019, several publications reported ZnO nanoparticles synthesized using leaf extract of various plants, e.g., Eucalyptus globulus Labill [88], Cassia fistula and Melia azadarach [89], Euphorbia hirta [90], saffron leaf [91], Azadirachta Indica [92], Aquilegia pubiflora [93], Broccoli extract [94], Costus igneus [95], Pandanus odorifer [96], and Solanum torvum [97]. Roots and roots' extracts are also well established for the synthesis of ZnO nanoparticles. To date, different roots' extracts have been used for the synthesis of ZnO nanoparticles, as shown in Table 2. In 2021, the synthesis of spherical ZnO nanoparticles with an average size of 11.34 nm using Rubus Fairholmianus root (Dimethyl sulfoxide) extract was reported and tested against S. aureus (MIC = 157.22 µg/mL) [98]. In another study, aqueous root hair extract of Phoenix dactylifera was utilized for the synthesis of ZnO nanoparticles with a size range of 30.87 to 47.89 nm. ZnO nanoparticles were found to be 45% more cytotoxic than well-known chemotherapeutic drugs (doxorubicin). Especially Triple-negative breast cancer cells were found to be weaker to Phoenix dactylifera-mediated nanoparticles than doxorubicin. Phoenix dactylifera-mediated were observed to be 82.26% cytotoxic to lungs cancer cells. Phoenix dactylifera-mediated ZnO nanoparticles exhibited promising antibacterial action against K. pneumoniae (ZOI = 2.4 cm), S. aureus (ZOI = 3.0 cm), Salmonella typhi (ZOI = 2.8 cm), and E. coli (ZOI = 2.7 cm) [99]. Liu, Di, et al. reported Raphanus sativus-mediated ZnO nanoparticles exhibited antibacterial activity against S. aureus (ZOI = 21.23 ± 1.16 mm) and E. Faecalis (ZOI = 11.23 ± 0.58 mm) [100]. Recently, Sphagneticola trilobata L was also reported to synthesize ZnO nanoparticles, which were mainly irregular in shape [101]. Moringa oleifera was applied for the formation of hexagonal-shaped ZnO nanoparticles with a size of~25 nm. The prepared ZnO nanoparticles were tested for their antibacterial action against B. Subtilis (ZOI = 12.5 mm) and E. coli (ZOI = 11.6 cm) [102]. Biosynthesis of ZnO nanoparticles using stem or stem bark has gained immense attention recently. Synthesis of ZnO nanoparticles using stem and stem bark is shown in Table 3. Prepared ZnO nanoparticles exhibited an excellent inhibitory effect on cancer line cells, whereas they had no hazardous effect on normal line cells. Amygdalus scopariamediated ZnO-cured diabetic rats illustrated an excellently higher level of insulin and lower alanine transaminase (ALT), aspartate aminotransferase (AST), and blood glucose as compared to a Streptozotocin (STZ)-induced diabetic group and other cured groups [103]. Cinnamomum verum bark was reported for the formation of ZnO nanoparticles and tested against S. aureus (MIC = 125 µg/mL) and E. coli (MIC = 62.5 µg/mL) [104]. Hexagonally shaped ZnO nanoparticles were synthesized by using aqueous root extract of Mussaenda frondosa with a size range of 5-20 nm, and its antimicrobial efficiency was evaluated against S. aureus (ZOI = 21.51 mm), B. subtilis (ZOI = 19.13 mm), and P. aeruginosa (ZOI = 20.31 mm). This study reported photocatalytic activity and biological applications such as antidiabetic, anticancerous, antioxidant, anti-inflammatory, and antimicrobial activity [105]. Albizia lebbeck aqueous stem bark extracts were utilized for the formation of ZnO nanoparticles and tested against S. aureus (ZOI = 4.50 ± 0.30 mm), B. cereus (ZOI = 8.83 ± 0.42 mm), S. typhi (ZOI = 91.3 ± 0.41mm), K. pneumoniae (ZOI = 7.30 ± 0.29 mm), and E. coli (ZOI = 10.57 ± 0.320 mm). The Albizia lebbeck stem bark extracts-mediated ZnO nanoparticles exhibited strong antioxidant and cytotoxicity against breast cancer cell lines [106].  Flowers were also used in the biosynthesis of ZnO nanoparticles, as shown in Table 4. Biological synthesis of flake-structured ZnO nanoparticles was achieved by using Cassia auriculata. The prepared ZnO nanoparticles were used against various bacterial strains to evaluate their antimicrobial efficiency against S. pneumonia, S. aureus, E. coli, and K. pneumonia (the size of the zone observed ranged from 18 mm to 25 mm against the abovementioned pathogens) and anticancer agent against MG-63 cell. The cell adhesion assay was carried out to investigate the anticancer efficiency of Cassia auriculata-mediated ZnO nanoparticles against MG-63 cells [107]. In another study, the antimicrobial efficacy of Punica granatum flower-mediated ZnO nanoparticles was assessed against S. diarizonae (ZOI = 10.00 mm), B. cereus (ZOI = 12.33 ± 0.58 mm), S. aureus (ZOI = 10.50 ± 0.87 mm), P. aeruginosa (ZOI = 10.00 ± 1.00 mm), S. pneumonia (ZOI = 14.00 ± 1.00 mm), K. pneumonia (ZOI = 11.00 ± 1.00 mm), E. faecalis (ZOI = 9.67 ± 0.58 mm), S. typhi (ZOI = 8.67 ± 1.15 mm), E. coli (ZOI = 10.00 ± 1.00 mm), L. monocytogenes (ZOI = 14.33 ± 0.58 mm), E. faecium (ZOI = 15.83 ± 0.76 mm), A. hydrophila (ZOI = 13.83 ± 0.29 mm), and M. catarrhalis (ZOI = 12.00 ± 1.00 mm) [108]. Moringa Oleifera aqueous flower extract was used for the production of ZnO nanoparticles with a size of 13.2 nm [109]. Matricaria chamomilla L promoted the preparation of ZnO nanoparticles with an average size of 62 nm, reported by Ogunyemi, Solabomi Olaitan, et al. [110]. Hexagonally and Triangularly shaped ZnO nanoparticles with size range 30 to 40 nm synthesized by using the flower of Syzygium aromaticum were reported by Lakshmeesha, Thimappa Ramachandrappa, et al. [111]. The aqueous seed extract of the different plants has been widely used as a reducing and capping agent for the biosynthesis of ZnO nanoparticles, as shown in Table 5. Ware, Umavathi, Saraswathi, et al. reported the ecofriendly synthesis of ZnO nanoparticles using seed extract of Parthenium hysterophorus with a size of 10 nm [112]. In another study, Lettuce aqueous seed extract was utilized as a reducing agent for the formation of ZnO nanoparticles with an average size of 50 nm, and its effect on the process of seed germination was investigated [113]. Ngom, I. et al. reported the formation of ZnO nanoparticles using seed extract of Moringa Oleifera [114]. Longan aqueous seed extract was employed for the production of pure hexagonal-phase ZnO nanoparticles with a size range of 10-100 nm. The photocatalytic activity of Longan seed-mediated ZnO nanoparticles was evaluated through de-colorization of Orange II, methylene blue (MB), and methyl orange [115]. Trigonella foenum-graecum aqueous seed extract was also successfully applied for the biosynthesis of irregular spherical and flake-shaped ZnO nanoparticles with a size range of 70 nm to 90 nm. The photocatalytic activity of trigonal Trigonella foenumgraecum-mediated ZnO nanoparticles was evaluated through de-colorization of methylene blue [116]. ZnO nanoparticles synthesized using fruit and fruit extract are shown in Table 6. Khan, Mujahid, et al. reported the synthesis of hexagonal ZnO nanoparticles with an average size of 58 nm using an aqueous extract of Passiflora foetida fruit peels. Passiflora foetidabased ZnO nanoparticles showed remarkable efficiency toward Rhodamine B and MB dye (91.06%) and MB dye (93.25%), respectively [117]. Aqueous fruit extracts of Myristica fragrans were used to prepare elliptical-and spherical-shaped ZnO nanoparticles with a mean size of 41.23 nm and tested against E. coli (ZOI = 15 ± 1.54 mm), K. pneumoniae (ZOI = 27 ± 1.73 mm), P. aeruginosa (ZOI = 17 ± 1.66 mm), and S. aureus (ZOI = 21 ± mm). Prepared nanoparticles exhibited excellent larvicidal activity against Aedes aegypti. Similarly, significant leishmanicidal activity was also examined against amastigote and promastigote parasites. The biologically prepared ZnO nanoparticles exhibited excellent antioxidant and biocompatible nanoparticles. Photocatalytic activities of prepared ZnO nanoparticles were evaluated through decolorizations of methylene blue [118]. Hexagonal ZnO nanoparticles with an average size of 33.1 ± 11.7 nm were derived from aqueous peel extract of citrus sinensis and tested against E. coli and S. aureus. The toxicity of citrus sinensis-based ZnO nanoparticles toward human umbilical vein endothelial cells was dosedependent. The feasibility of human umbilical vein endothelial cells (HUVECs) increased when reacted with 6.25 mg/L of prepared ZnO nanoparticles. However, feasibility lowered sharply, to around 20%, when the concentration of prepared ZnO nanoparticles increased to 25 mg/L or higher. It showed that prepared ZnO nanoparticles enhance the growth of HUVECs at low concentrations [119]. Aqueous fruit extract of orange was utilized for the formation of spherical ZnO nanoparticles with a size range of 10-20 nm and was evaluated against E. coli and S. aureus [120]. In another study, ZnO nanoparticles were prepared using the fruit of Ailanthus altissima with a size range of 5-18 nm and tested against E. coli and S. aureus [121].

Gold Nanoparticles
Among the various metal and metal oxide nanoparticles, gold nanoparticles have specific morphology (size, shape, and crystalline nature), controlled geometry, and stable nature [122]. Gold nanoparticles are utilized in light-harvesting assemblies, electronics, molecular switches, and sensing [123][124][125][126]. Gold nanoparticles are also utilized in the diagnosis, detection, and cure of various diseases [127,128]. Gold nanoparticles, with their multiple properties, gained attention and their features can be modified by altering the shape, size, and aspect ratio. Gold nanoparticles are proven to be exclusive in biomedical applications. They are used as a tool for early cancer diagnosis, heart diseases, and the presence of infectious agents. The non-toxic and biocompatible nature of gold nanoparticles makes them a good candidate for drug and gene delivery. They can modify their surface with antibodies and other drug molecules. They carry drugs that are released at the target site selectively [129,130]. Gold nanoparticles are also explored for gene delivery due to their optimal properties. It is reported that, for the enhancement of the genetic material of any plant, the DNA coated with gold nanoparticles is injected into the plant cell and results in transformation [131]. Gold nanoparticles, due to their biochemical inertness and their unique optical-electronical properties, are also broadly applied in analytical sciences. Sensory probes, conductors, electronic chips, photovoltaics, and fuel cells are advanced technical applications of gold nanoparticles. Gold nanoparticles are widely used in fluorescence, surface plasmon resonance, lateral flow immunochromatographic assay (LFICA), enzyme-linked immunosorbent assay (ELISA), and SERS immunoassays of biomolecules (Elahi, N.). The current advancement in imaging techniques such as Computed tomography, X-ray, and SERS is also based on the high-density resolution of gold nanoparticles. [132]. They are also found in many chemical reactions as a catalyst.

Synthesis of Gold Nanoparticles from Plant
Gold nanoparticles can be prepared from various parts of the plant such as leaf, Stem, root, flower, seed, and fruit. Synthesis and the mechanism of formation of gold nanoparticles using plant are illustrated in Figures 5 and 6, respectively.  Leaves' extracts are used to synthesize gold nanoparticles, as shown in Table 7. In 2021, gold nanoparticles were derived from aqueous leaf extract of Lantana camara, Populus alba, and Hibiscus arboreus with a size of~16.3 ± 0.7 nm. The antibacterial activity of prepared gold nanoparticles was tested against E. coli and S. aureus (MIC value = 100 µg/mL). The bio-synthesized gold nanoparticles were also utilized for the degradation of MB and CR dye [134]. In another report, Limnophila rugosa was used for the production of sphericalshaped gold nanoparticles with a mean particles' size distribution of 122 nm. Limnophila rugosa-capped gold nanoparticles showed tremendous catalytic activity in the reduction of different nitrophenols, e.g., 4-nitrophenol, 3-nitrophenol, and 1,4-nitrophenol [135]. Olajire, A.A. et al., reported the biological synthesis of spherical gold nanoparticles with a mean size of 18.85 ± 6.74 nm by utilizing aqueous leaf extract of Ananas comosus. Low-density polyethylene with 1% gold nanoparticles exhibited a degradation efficacy of 90% after 240 h [136]. Recently, a single-step and eco-friendly biosynthesis of gold nanoparticles was reported by El-Borady et al., utilizing leaf of Phragmites australis. The results exhibited the production of spherical-shaped gold nanoparticles with about 18 nm diameter. Phragmites australis-based gold nanoparticles showed tremendous anticancer efficiency with an IC 50. Prepared gold nanoparticles also exhibited good quenching for 2,2-diphenyl-1-picrylhydrazyl free radical with scavenging % equal to 10.26. Phragmites australis-based gold nanoparticles also showed excellent photocatalytic activity, as they completely degraded the MB in just 60 s. Mentha Longifolia-mediated nanoparticles had tremendous anti-breast cancer efficiency against HS319.T, MCF7, and UACC-3133 cell lines [137]. An environmentally friendly method for the biological formation of gold nanoparticles was developed by Shah, Sumaira, et al., using ethanol leaf extract of Sageretia theazans. The biological activity of Sageretia theazans-based gold nanoparticles was evaluated against S. au-reus, K. pneumonia, and B. subtilis. The antioxidant efficiency was investigated with DPPH scavenging activity; the maximum scavenging efficiency was observed at 100 µg/mL [138]. In another report, gold nanoparticles were bio-synthesized by reducing gold metal ions upon interlinking with aqueous leaf extract of Coriandrum sativum. TEM was utilized to calculate the size range of spherical gold nanoparticles, which was in the range of being 32.96 ± 5.25 nm [139]. In another study, an instantaneous, single-step, inexpensive, ecofriendly production of gold nanoparticles via aqueous leaf extract Persicaria salicifolia was reported by Hosny, Mohamed, et al., resulting in the production of violet-colored, spherical-shaped gold nanoparticles with diameters between 5 and 23 nm. The cytotoxicity study of Persicaria salicifolia-mediated gold nanoparticles using sulforhodamine-B assay showed tremendous cell capability in inhibiting the proliferation and growth of breast cancer cells (MCF7 cell line). Additionally, prepared gold nanoparticles showed antioxidant activity [140]. In 2021, gold nanoparticles were biosynthesized through the mixing of aqueous leaf extract of Curcumae Kwangsiensis with a size of~8-25 nm. Gold nanoparticles showed tremendous antioxidant properties toward common free radicals, e.g., DPPH. Prepared gold nanoparticles had excellent anti-ovarian cancer activity against Sw-626, SK-0V, and P cell lines [141]. In another study, the aqueous extract Centaurea behen was utilized for the simple and environmental production of gold nanoparticles. For testing of the cytotoxicity effect of C. behen extract and gold nanoparticles, an MTT test was performed. C. behen-mediated gold nanoparticles revealed the cytotoxicity against THP-1 cell line. The IC 50 for prepared nanoparticles was measured for about 25 µg/mL, whereas C. behen extract could not achieve the IC 50 . Similarly, for testing of antioxidant property of gold nanoparticles, a DPPH test was performed. Gold nanoparticles revealed maximum DPPH scavenging efficiency of 14% [142]. Padalia   2019 [154] In 2019-2020, several publications reported gold nanoparticles synthesized using leaf extract of various plants, e.g., Jasminum auriculatum [144], Vitex negundo [145], Pongamia pinnata [146], Lactuca indica [147], Croton Caudatus [148], Sansevieria roxburghiana [149], Simarouba glauca [150], Alcea rosea [151], Bauhinia pupurea [152], Coleus aromaticus [153], and Annona muricata [154]. The seed extract of the different plants has been widely used as a reducing and capping agent for the biosynthesis of gold nanoparticles, as shown in Table 8 Licorice-based gold nanoparticles exhibited antioxidant activity toward DPPH and ABTS. The cytotoxicity of prepared particles was examined by utilizing the MTT approach against liver (HePG-2) and breast cancer (MCF-7) cell lines [155]. In another research, the author adopted an environmentally friendly and sustainable method to synthesize gold nanoparticles by utilizing Phragmites australis aqueous root extract. The cytotoxicity of prepared particles was examined by utilizing an MTT approach against human lung cancer cells (A549 cell line). Antioxidant efficiency was less than 10%. The prepared gold nanoparticles showed excellent efficiency in removing methyl orange and methyl blue [156]. In 2020, spherical gold nanoparticles were derived by a green method utilizing Codonopsis pilosula with the size of 20 ± 3.2 nm and tested against E. coli (ZOI = 7.0 ± 0.42 mm), B. subtilis (ZOI = 12.0 ± 0.85 mm), and S. aureus (ZOI = 17.0 ± 1.2 mm) [157]. Zhang, Tipeng, et al. prepared the gold nanoparticles using Euphorbia fischeriana aqueous root extract with the size of 20-60 nm [158]. In 2019, Paeonia moutan methanol root extract was used to synthesize gold nanoparticles. The cytotoxicity of prepared particles was examined by utilizing an MTT approach against the murine microglial (BV2) cells. Paeonia moutan-mediated gold nanoparticles hindered the inflammation in murine microglial (BV2) [159]. Recently, Brassica oleracea var. Acephala cv galega was utilized to biosynthesize spherical gold nanoparticles with an average diameter of 25.08 ± 3.73 nm, as shown in Table 9. Additionally, the antioxidant assay was carried out in the root extract after the formation of gold nanoparticles [160]. Khoshnamvand, M. et al., reported the synthesis of gold nanoparticles by utilizing Apium graveolens aqueous stem extract. The prepared particles could be utilized as a catalyst for the reduction of 4-nitophenol [161]. Gold nanoparticles were biosynthesized utilizing the stem of Angelica aiges by a green approach. Prepared particles degraded the Malachite and eosin dye [162]. In 2021, saffron stigma-mediated gold nanoparticles were produced by Alhumaydhi, Fahad A., et al. and tested against E. coli, as shown in Table 10 [163]. In 2020, spherical gold nanoparticles were derived from Clitoria ternatea, having particles size of 18.16 nm [164].  Table 11. TEM exhibited the biosynthesized gold nanoparticles to be 16.63 nm in size and spherical [166].

Silver Nanoparticles
The synthesis of silver nanoparticles has gained remarkable attention due to their application in climate change, contamination [167], anti-microbial activities [168,169], information storage [170], bio-medical applications [171], energy generation [172], clean water technology [173], catalysis [174], biological sensors [175,176], optoelectronics [177], Lithium-ion batteries [178], and DNA sequencing [179]. Silver nanoparticles have vast applications in biomedicine due to their unique biological properties depending on their structure and size. Silver nanoparticles possess a very wide-spectrum, high antimicrobial activity [180]. They effectively kill microbes at a very low concentration [181]. Silver nanoparticles from free radicals alter the properties of microbial membranes and ultimately cause damage. Silver nanoparticles interact with microbial DNA and inhibit microbial activities [182]. Medical applications of silver nanoparticles are not only limited to antimicrobial treatments but they are also extended to bone healing [183], wound healing, vaccine development, the anti-diabetic effect [184], etc. Recent studies also proved silver nanoparticles as efficient candidates against various cancers. The surface-to-volume ratio of silver nanoparticles affects anticancer activity. Strong anticancer activities of silver particles are reported when size is reduced to even Angstrom [185]. It is also used in the treatment to control multi-drug-resistant microorganisms [186]. Silver nanoparticles are also used as a tool in dentistry [187,188]. Apart from biomedical applications, silver nanoparticles are widely used in various analytical techniques because of their unique physicochemical properties. They play an important role in biosensor and imaging technologies [189]. Many analytical techniques are also using silver nanoparticles in instrumentation [190]. They are used as fillers in biomaterials. Silver nanoparticles' films have been recently used as an alternative food packaging material [191]. There are various methods, such as Supercritical Fluid Synthesis, Laser Ablation, Laser Pyrolysis, Ball Milling, Ultrasonic Synthesis, etc., that have been used for the synthesis of silver nanoparticles. Recently, the biological synthesis of silver nanoparticles by using biological organisms such as plants, fungi, algae, and bacteria as capping and reducing agents and their anti-microbial activity has been studied. The different biological molecules such as tannins, ketones, flavonoids, protein, and aldehydes are responsible for the synthesis of silver nanoparticles by oxidation of Ag + to Ag 0 .

Synthesis of Silver Nanoparticles
Silver nanoparticles can be prepared from various parts of the plant such as leaf, stem, root, flower, seed, and fruit.

Synthesis of Silver Nanoparticles Using Flower Extracts:(2021)
Flowers were also used in the biosynthesis of silver nanoparticles, as shown in Table 16. In 2021, biosynthesis of silver nanoparticles with a mean size of 7.6 nm was conducted utilizing Avera lanata. The DPPH radical scavenging analysis showed the antioxidant activity of prepared silver nanoparticles [260]. A rapid, facile, sustainable, and controlled process was reported for the synthesis of silver nanoparticles by utilizing Fraxinus excelsior aqueous and ethanolic flower extract. The prepared silver nanoparticles can be used as an environmentally friendly material for the coloration of woven glass fabrics [261]. Aravind, M., et al. derived silver nanoparticles with an average size of 40 nm utilizing jasmine aqueous extract (flower) and tested them against S. aureus and E. coli. The abovementioned prepared silver nanoparticles degraded the MB [262].

Titanium Oxide Nanoparticles
Titania (existing as TiO 2 nanoparticles) constitutes specific thermal, magnetic, optical, and electric properties. Normally, Titanium oxide existed in three forms e.g., brookite crystalline polymorphs' form, anatase form, and rutile form. The most important applications of TiO 2 are photocatalytic degradation and splitting [263], electronic and electrochromic [264], sensing instruments [265], and photovoltaic cells [266]. Among all other metal nanoparticles' oxide, titanium oxide nanoparticles showed distinctive morphologies (size, shape, and texture) and surface chemistry. It is utilized in the preparation of papers, foodstuff, tints, cosmetics, and medicine [267]. Colloidal titanium oxide nanoparticles are utilized in the degradation of hazardous chemicals in water [268,269]. Conventionally, titanium oxide nanoparticles are prepared using chemical and physical techniques, e.g., chemical precipitation, chemical vapor deposition, sol-gel, and hydrothermal [270]. All these conventional approaches require high pressure, temperature, and toxic chemicals [271]. However, environmentally friendly, rapid, and inexpensive methods are required to prepare nanoparticles on a larger scale with lesser toxicity [272]. This could be only possible by utilizing biological extract (plants, bacteria, algae, and fungi) through green chemistry.
Synthesis of Titanium Oxide Nanoparticles from Leaves, Roots, Flowers, Seeds, and Fruit Peel Extracts: (2019-2021) Among the biological extracts, plants are considered as one of the most favorable agents for the preparation of titanium oxide nanoparticles, as shown in Table 17. Various types of phytochemicals (phenol, amino acid, carbohydrate, and flavonoid) in plants regulate the biosynthesis of titanium oxide nanoparticles through stabilization and reduction processes [273]. The reaction starts strenuously when a titanium salt (precursor) is mixed with plant extract and color change (light-green to dark) shows the first sign of biosynthesis of titanium oxide, as shown in Figure 7 [274]. Synthesis of titanium oxide nanoparticles using various parts of plant is shown in Table 18.

Copper and Copper Oxide Nanoparticles
Among all metal or metal oxide nanoparticles, copper oxide nanoparticles get more interest due to their multiple applications [289]. Copper oxide is a p-type semiconductor having a narrow bandgap of 1.7 eV. [290]. Biomedical applications of copper oxide nanoparticles involved antifouling, antioxidant, anti-microbial targeted drug delivery, and antibiotics. Copper oxide nanoparticles also have applications in other fields of science such as gas sensors, environmental remediation, nanocomposites' synthesis, magneto-resistant material, textiles, high-temperature superconductor, and conducting material [291][292][293][294]. Various physiochemical methods have been extensively used to prepare copper oxide nanoparticles [295]. However, these methods have some flaws, e.g., releasing different hazardous chemicals, time consuming, and high cost. Thus, there is a need for a simple, quicker, eco-friendly, and inexpensive method to prepare nanoparticles with phase selectivity, purity, and homogeneity in morphology [296]. Biological synthesized copper oxide nanoparticles exhibited excellent anti-microbial activity [297]. Green approaches have led to developing a simple, cost-effective, and environmentally friendly process for the biosynthesis of nanoparticles [298].
Synthesis of Copper and Copper Oxide Nanoparticles Using Leaves, Seeds, Flower, and Fruit Peel Extracts: (2019-2021) Plants create various secondary metabolites and consist of phytochemicals, which are excellent bioresources for the fabrication of copper and copper oxide nanoparticles ( Table 18). The most favorable phytochemicals in plants are flavonoids and phenols, present in various parts of the plant, i.e., stems, leaves, fruits, seeds, and flowers. These phenolic phytochemicals have ketone and hydroxyl groups, taking part in the iron chelation and subsequently describing an excellent antioxidant activity [299]. Nanoparticles synthesized through this green approach increase instability, fend off the deformation and agglomeration of nanoparticles, and increase the phenomena of adsorption of phytochemicals on the nanoparticles' surface, which increase the reaction rate of nanoparticles [300]. One of the common approaches in preparing copper and copper oxide nanoparticles is mixing a stoichiometric concentration of plant extract to a stoichiometric concentration of copper salt, heating the nano solution to a suitable temperature, with contentious stirring (shown in Figure 8). The mechanism of formation of copper oxide nanoparticles is shown in Figure 9.

Iron or Iron Oxide Nanoparticles
The structure of nanoparticles contains the magnetic core and their combinations, which have magnetic features in the presence of a textan erior magnetic field. Various types of iron oxide nanoparticles, each with its peculiar properties, magnetic behavior, formulas, and applications. The magnetic behavior is because of the motion of electrons [319]. Depending on the response to an external magnetic field, there are six types of material: super magnetic, ferromagnetic, diamagnetic, paramagnetic, antiferromagnetic, and ferrimagnetic. Due to the presence of one electron in the third sub-shell of intermediate metals, e.g., cobalt, iron, and nickel, which is in the absence of an external magnetic field, ferromagnetism behavior is produced [320]. Magnetic property is also exhibited by Ferromagnetic material. Paramagnetic and magnetic phenomena are also reported among magnetic materials. Because of the superparamagnetic feature of the magnetic nanocatalyst, these nanoparticles have been utilized in various fields. These nanoparticles consist of gadolinium, nickel, cobalt, iron metal, and metal oxide, e.g., Fe 2 O 3 [321]. Among different types of metal and metal oxide nanoparticles, iron and iron oxide nanoparticles have exhibited high efficiency in various biomedical and industrial applications. There are eight types of iron oxide nanoparticles, among which magnetite, hematite, and maghemite have very useful applicants. Each of these three oxides has specific catalytic, magnetic, and biochemical properties. Hematite is extensively utilized in pigments, catalysts, and catalysis. It is also a reagent for the preparation of magnetite and maghemite, which have been kept in sight for various applications.
Synthesis of Iron and Iron Oxide Nanoparticles from Leaf, Flower, Seed, and Fruit Extracts: (2019-2021) Different and cost-efficient synthesis processes have been used by utilizing plants, as shown in Table 19. Synthesis of iron or iron oxides nanoparticles using plants are showed in Figure 10. Arjaghi, Shayan Khalili, et al. synthesized the spherical iron oxide nanoparticles with a size range of 20-70 nm by utilizing Ramalina sinensis [322]. In another report, Chlorophytum comosum aqueous leaf extract was utilized for the biosynthesis of iron nanoparticles with a size of 100 nm and tested against P. aeruginosa, E. faecalis, E. coli, and S. aureus. The prepared iron nanoparticles showed Methyl orange degradation (77% after 7 h) [323]. Jamzad, Mina, et al. carried out an experiment to derive spherical and hexagonal iron oxide nanoparticles utilizing Laurus nobilis and tested them against E. coli (ZOI = No), L. monocytogenes (ZOI = 12 mm), S. aureus (ZOI = No), P. spinulosum (ZOI = 14 mm), and A. aspergillus (ZOI = 13 mm) [324]. In 2020, Bhuiyan, Md Shakhawat Hossen, et al. reported the biosynthesis of iron oxide nanoparticles by utilizing Carica papaya aqueous leaf extract and tested them against S. aureus (ZOI = 14 mm), Klebsiella spp (ZOI = 9 mm), and E. coli (ZOI = 9 mm). The prepared iron oxide nanoparticles were tested against BHK-21 and Hela cell lines [325]. Vitta, Yosmery, et al. achieved iron nanoparticles from Eucalyptus robusta aqueous leaf extract and tested their antimicrobial commotion against S. aureus (ZOI = 1.15 ± 0.05 mm), B. subtilis (ZOI = 3.60 ± 0.40 mm), P. aeruginosa (ZOI = 29 ± 0.03 mm), and E. coli (ZOI = 1.10 ± 0.10 mm) [326]. In 2019, iron oxide nanoparticles with an average size of 52.78 nm were synthesized utilizing Ruellia tuberosa aqueous leaf extract and tested against K. pneumoniae (ZOI = 12 mm) and E. coli (ZOI = 17 mm) [327]. In 2021, Avicennia marine aqueous flower extract was utilized to synthesize iron oxide nanoparticles with an average size of 30-100 nm [328]. Semi-spherical Iron oxide nanoparticles with a size range of 25 to 55 nm were prepared through a green process utilizing Punica granatum seed. The prepared iron oxide nanoparticles exhibited efficient degradation toward reactive blue (95.08% after 56 min) [329]. An eco-friendly biosynthesis of iron oxide nanoparticles utilizing Borassus flabellifer ethanol seed coat extract was reported by Sandhya et al. and was tested against B. subtilis, E. coli, S. aureus, C. albicans, and A. niger [330]. Aziz

Cobalt and Cobalt Oxide Nanoparticles
Cobalt is a transition (d-block) metal that has useful effects on human health [333,334]. It is an essential part of Cobalamin (Vitamin B12), which is helpful in the cure of anemia as it excites the production of red blood cells [334]. Cobalt has unique catalytic, electrical, and optical properties that make it favorable for a vast range of applications involving catalysts, nano-electronic devices, and nano-sensors [335]. Cobalt can show variable oxidation states, e.g., CO 4+ , CO 3+ , and CO 2+ , that make it favorable to be utilized in various fields [336]. Now, cobalt nanoparticles have attracted remarkable interest because they are cheaper than other metal or metal oxide nanoparticles and exhibit various properties, e.g., magnetic and electrical, because of their huge surface area [337,338].

Synthesis of Cobalt or Cobalt Oxide Nanoparticles Using Plants
Synthesis of cobalt and cobalt oxide nanoparticles by a green approach utilizing plants, in general, includes washing or drying the plants' part (leaves, root, stem, flower, seed, and fruit), as shown in Table 20. The plant materials (fresh or powder) are boiled with water and the resultant extract is filtered. Phytochemical properties are because of the presence of biomolecules in plant extracts, e.g., vitamin, phenol, protein, carbohydrate, flavonoid, and more. Adding cobalt salt to plant extract reduces and stabilizes the cobalt ion to prepare cobalt and cobalt oxide nanoparticles [339].

Antibacterial Activities of Metal and Metal Oxide Nanoparticles
Research is going on and a vast amount of literature exists on the antimicrobial activity of metal and metal oxide nanoparticles. The silver nanoparticles excellently discompose the polymer sub-units of the cell membrane in micro-organisms. The plant-mediated silver nanoparticles consequently rupture the cell membrane, destroying the protein synthesis mechanism in the bacteria [346]. The higher concentration of silver nanoparticles has rapid membrane permeability, as compared to a lower concentration, and subsequently breaks the cell wall of bacteria, as shown in Figure 11 [347]. The highest conductivity was seen in Rhizophora apiculate-reduced silver nanoparticles, which exhibited a lower number of a bacterial colony in the experimental plate than the silver nitrate-treated cells, which may be because of a larger surface area and smaller size of nanoparticles. These two factors increase the permeability across the cell membrane and cell destruction [348]. The green-synthesized silver nanoparticles were prepared using Citrus sinensis peel extract and evaluated for antibacterial activity toward S. aureus, P. aeruginosa, and E. coli [349].

Antifungal Activity
The fungicidal mechanism of plant-mediated metal and metal oxide nanoparticles has greater potential as compared to commercial antibiotics, e.g., amphotericin. The plantmediated silver nanoparticles have clearly exhibited the membrane breakage in Candida sp. and damage in fungal components (intercellular) and, consequently, cell function was destroyed [350]. Most commercial drugs have limited clinical applications and have more adverse effects. Consequently, the commercial antifungal agents induce side effects, e.g., liver damage and renal failure and nausea, diarrhea, and body temperature increased after utilizing the drugs. The cell wall of fungi is made up of protein and fatty acid. The plant-mediated silver nanoparticles have promising activity toward spore-producing fungus and efficiently damage the fungal growth. In the fungal cell membrane composition and structure, significant changes were seen by interacting it with metal and metal oxide nanoparticles [351].

Anticancer Activity
Cancer is an uncontrollable cell proliferation, having extensive changes of enzymatic parameters and bio-chemicals, which is the universal behavior of cancer cells. The overexposure of cellular growth will be triggered, and the cell cycle mechanism in cancerous cells will be arrested by utilizing plant-based nanoparticles [352]. The plant-based metal or metal oxide nanoparticles have excellent effects on different cancer cell lines, e.g., Hela, Hep 2, and HCT 116 cell lines. To date, various works reported that plant-mediated nanoparticles have the ability to control cancer cell growth. The bettered cytotoxic effect is because of secondary metabolites and some other non-metal composition in the prepared medium [353,354]. The bio-synthesized silver nanoparticles triggered the cell cycle and enzymes in the bloodstream [355]. Furthermore, the plant-derived nanoparticles control the formation of free radicals from the cell. Free radicals normally are the cause of cell proliferation and harm normal cell function. The moderate quantity of gold nanoparticles is the cause of the apoptosis mechanism in tumor cells (malignant cells) [356]. The metal and metal oxide nanoparticles have proven their application in medical science to diagnose and cure different types of cancer cells. The plant-mediated nanoparticles are advanced and revolutionized to cure the malignant deposits without disturbing the normal cell line.

Challenge and Future Perspectives of Plant-Mediated Metal and Metal Oxide Nanoparticles
To date, various plants' extracts have been investigated for the preparation of metal or metal oxide nanoparticles and have been excellently used in a wide range of applications due to their huge abundance in nature. Recently, plant extracts have been investigated for their effectiveness in the formation of nanoparticles, which are based on the compositions of diverse phytochemicals and plant sources. However, the specific phytochemicals causing the reduction, capping, and stabilization of nanoparticles in the green synthesis mechanism are still not completely understood. Thus, further studies are required to understand these details. A suggested approach that might be able to describe the responsible phytochemicals serving as stabilizing and reducing candidates involves isolation protocols of the pure compound to identify specific phytochemicals. Additionally, the composition of phytochemicals in plant extract can be determined through various analytical techniques, e.g., ICP-AES (Inductively coupled plasma-atomic emission spectroscopy), HPLC (High Pressure Liquid Chromatography), NMR (Nuclear magnetic resonance), and GC-MS (gas chromatography-Mass spectroscopy) and various quantitative and qualitative chemical processes can be utilized to know the variety of phytochemicals through Coomassie blue assays, phenol-sulfuric acid assays, and colorimetric assays. The main challenge may be in knowing the basic profile of bio-molecules needed for serving as reducing agents of metal ions. Despite the various benefits of plant extracts, there are many other hindrances that should be accounted for before they can be applied practically, e.g., structure, control of shape, size, monodispersity, and crystallinity of plant-mediated nanoparticles. This template morphology is also connected to the phytochemicals that exist in the plant extract. Additionally, some other factors affect the morphology of nanoparticles such as metal ion concentration, reaction temperature, plant extract concentration, and pH. Furthermore, as described, the capability to attain a high yield of nanoparticles is also influenced, as is the reduction power of the plant.
The stability of plant-mediated nanoparticles is another important parameter to consider. It is very necessary to ensure that plant-mediated nanoparticles can remain stable for a long time without any changes in morphology. Another condition that should be discussed is an estimation of toxicity and biocompatibility of plant-mediated nanoparticles to human health and the ecosystem, which are still not described efficiently and are frequently reported.
More integrated, detailed, and systematic research work is still needed to fully define the human and ecological toxicity profile of plant-mediated nanoparticles to develop a stable system for the preparation of nanoparticles with well-defined size, morphology, and efficient homogeneity.

Conclusions
Biosynthesis of metal and metal oxide nanoparticles has been advanced and is a highly attractive research field of science over the last decades. Thus, knowledge of green chemistry and the use of green routes for the synthesis of nanoparticles is increasing day by day in order to get an environmentally friendly process. Various types of natural extracts (such as plants, fungi, algae, and bacteria) have been utilized for the preparation of nanoparticles. Among all the above mentioned sources, plants have been considered to possess remarkable efficiency as capping, reducing, and stabilizing agents for the preparation of nanoparticles with desired morphology due to the presence of Phytomolecules. This review delivers an excellent platform to researchers or the scientific community to gain diverse information related to detailing green synthesis of metal or metal oxide nanoparticles using multiple plant parts. Fundamentally, the greener production of metal or metal oxide nanoparticles using plant extracts has different biological applications such as anticancer, anti-microbial, and antifungal activity. Acknowledgments: All authors acknowledge the School of Chemistry, Minhaj University Lahore for providing platform for this work.

Conflicts of Interest:
The authors declare that they have no known competing financial interest or personal relationships that could have appeared to influence the work reported in this paper.