Green Synthesis of Bioinspired Nanoparticles Mediated from Plant Extracts of Asteraceae Family for Potential Biological Applications

The Asteraceae family is one of the largest families in the plant kingdom with many of them extensively used for significant traditional and medicinal values. Being a rich source of various phytochemicals, they have found numerous applications in various biological fields and have been extensively used for therapeutic purposes. Owing to its potential phytochemicals present and biological activity, these plants have found their way into pharmaceutical industry as well as in various aspects of nanotechnology such as green synthesis of metal oxide nanoparticles. The nanoparticles developed from the plants of Asteraceae family are highly stable, less expensive, non-toxic, and eco-friendly. Synthesized Asteraceae-mediated nanoparticles have extensive applications in antibacterial, antifungal, antioxidant, anticancer, antidiabetic, and photocatalytic degradation activities. This current review provides an opportunity to understand the recent trend to design and develop strategies for advanced nanoparticles through green synthesis. Here, the review discussed about the plant parts, extraction methods, synthesis, solvents utilized, phytochemicals involved optimization conditions, characterization techniques, and toxicity of nanoparticles using species of Asteraceae and their potential applications for human welfare. Constraints and future prospects for green synthesis of nanoparticles from members of the Asteraceae family are summarized.


Introduction
The Asteraceae (Aster, Compositae, Daisy) family represents around 1600 genera, of which around 80 are reported for nanoparticle synthesis. Asteraceae is a sophisticated and botanically immensely specialized family containing mostly herbs. They are found in the tropics and tropical and warm areas of South, Southeast, and East Asia, Africa, Madagascar, and Central South America. Several of the genera in this family, such as Aster, Helianthus, Chrysanthemum, and Tagetes, are ornamentals, most of which have therapeutic properties. Many members of this family are used in medicine. Some are commonly planted in the field for vegetable and nutritional purposes. The order Asterales is made up of a single family, the sunflower family, which is the biggest of all plant families, with approximately 20,000 species. The Asteraceae is not only a vast and widespread family, but      [112] Note: UV-Vis: UV-Visible spectrophotometry; SEM: scanning electron microscopy; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; STEM: scanning transmission electron microscopy; SAED: selected area electron diffraction; XRD: X-ray crystallography; EDAX: energy dispersive X-ray analysis; DT-TGA: differential thermo gravimetric analysis; FTIR: Fourier transform infrared spectroscopy; TGA: thermal gravimetric analysis; DSC: differential scanning calorimetry; DTA: differential thermal analysis; TXRF: total reflection X-ray fluorescence; PPMS: physical property measurement system; VSM: vibrating sample temperature; EDXRF: energy dispersive X-ray fluorescences; BET: Brunau-Emmet-Teller analysis; XPS: X-ray photoelectron spectroscopy; AFM: atomic force microscopy; DLS: dynamic light scattering method; nm: nanometer; DW: distilled water; DDW: double distilled water; DiW: deionized water; SPR: surface plasmon resonance-: not available.     Antimicrobial, anticancer, and photocatalytic activity [145] Note: UV-Vis: UV-Visible spectrophotometry; SEM: scanning electron microscopy; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; STEM: scanning transmission electron microscopy; SAED: selected area electron diffraction; XRD:X-ray crystallography; EDAX: energy dispersive X-ray analysis; DT-TGA: differential thermo gravimetric analysis; FTIR: Fourier transform infrared spectroscopy; TGA: thermal gravimetric analysis; DSC: differential scanning calorimetry; DTA: differential thermal analysis; TXRF: total reflection X-ray fluorescence; PPMS: physical property measurement system; VSM: vibrating sample temperature; EDXRF: energy dispersive X-ray fluorescence; BET: Brunau-Emmet-Teller analysis; XPS: X-ray photoelectron spectroscopy; AFM: atomic force microscopy; DLS: dynamic light scattering method; nm: nanometer; DW: distilled water; DDW: double distilled water; DiW: deionized water; SPR: surface plasmon resonance-: not available.

Plant Material Used
Roots, stems, leaves, fruits, flowers, and seeds of Asteraceae members were used for the synthesis of NPs. The parts which are used to synthesize the nanoparticle could be washed and heated using a solvent. Researchers reported that both fresh and dried samples could be used to synthesize NPs. Dried samples at room temperature go through the process of weighing and crushing. Using Whatman filter paper, solutions are filtered, and clear solutions are used for synthesis [107]. Several studies report NPs being successfully synthesized from leaves of Acanthospermum hispidum, [17], the stem of Matricaria recutita [65], roots of Pechuelloeschea leubnitziae [69], the flower of Rhanterium epapposum [72], and seeds of Silybum marianum [77], etc., of Asteraceae members.

Extraction Methods
Extraction is the first and crucial step in the production of NPs. It happens when the solvent is diffused into plant tissues and solubilized phytochemicals with similar polarity and also these phytochemicals in the plant extract function as biocatalysts. The plant extract can be extracted using different methods such as maceration, soaking, soxhlet, reflux, sonication, heating, and boiling methods. Maceration was used to prepare an aqueous extract of Solidago canadensis to synthesize gold NPs [103]. Leaf extracts of Spilanthes calva were prepared using a boiling method to synthesize silver NPs [146]. To synthesize silver NPs from the leaf extract of Tragopogon collinus both the soaking and boiling methods were used [88].

Solvents Used
The solvent-free synthesis is not achievable in nanoparticle synthesis, since solvents have a crucial role in transferring the heat, dissolving solids, purification, and isolation steps, and altering viscosity. In green synthesis, the solvent is used in large amounts when compared to other materials, so the choice of solvent is essential, and also the types of solvents used during extraction significantly affect the amount of reducing agents extracted. Benzene is proven to be the best solvent but cannot be used in the synthesis of NPs due to its carcinogenic nature. Predominantly distilled water in addition to organic solvents such as ethanol and methanol are used to prepare extracts for the NPs synthesis from Asteraceae members. Among all the solvents, water is the best choice for the synthesis of NPs as it is non-toxic, eco-friendly, non-flammable, and economically feasible [147]. Tagetes erecta aqueous extracts were used for nickel NPs synthesis [141]. However, methanol and ethanol extract is used to synthesize silver nanoparticles from Tragopogon collinus [88].

Phytochemicals Involved
It is reported that the phytochemicals such as ketones, aldehydes, tannins, flavonoids, amides, terpenoids, and carboxylic acids in the plant are in charge of metal ion reduction ( Figure 2). The compounds in the plant extract components, are capable of electron donation, causing metal ion reduction to NPs. Plant extract concentration also depends on the solvent used for the extraction process. Tannins help in the production of silver NPs by acting as reducing and capping agents and also water-soluble secondary metabolites such as proteins, amino acids, and phenol control the biosynthesis of silver NPs. Several studies report plant extract and phytochemical concentrations affecting the size, shape, and application of the nanoparticle [148]. Tragopogon collinus extract containing phenolic compounds play a prominent role in the production of NPs [88]. In UV spectrum analysis, the aqueous leaf extract of Bidens pilosa, Galinsoga parviflora, and Conyza bonariensis showed absorbance peaks at 288 nm, 267 nm, and 286 nm, respectively. These peaks confirmed the presence of sugars, polyphenols, and amino acids, helpful in Fe ions reduction to Fe NPs [128].

Nanoparticle Synthesis from Asteraceae species
A large number of Asteraceae members have been utilized for the synthesis of various nanoparticles such as gold, silver, iron, copper, etc. For example, silver NPs synthesized from Asteraceae family members have significant catalytic action, atomic behavior, and biochemical reactivity due to large surface area. Recognition, reduction, limited nucleation, and growth help in the formation of silver NPs. In the recognition stage, the metal ions will be trapped on the surface protein of the plant extract by electrostatic interaction. Thereafter, proteins present in the extract reduce the Ag+ ions to Ag 0 by changing the secondary structure of the protein. This causes Ag ions reduction and accumulation in nuclei. The linkage of protein and a large number of biomolecules in the solution may lead to isotropic growth and the production of stable NPs [149].
The NPs synthesized by the addition of silver solution to the extract via. the green method is detected by color change. The color change is an indicator of the Ag ions reduction to Ag NPs by the plant extract phytochemicals. Briefly, the phytochemical compounds such as polyphenols, terpenoids, etc., present in the extract of Asteraceae members, donate electrons to reduce metal ions and form zero-valent metal atoms. Eventually, the collision of metal atoms with these atoms in the mixture results in the formation of several atoms with a stable core. These atoms will perform as nucleation regions and will form clusters that will continue to grow till an active supply of atoms, results in NPs formation. The process is carried out by the reduction of metal ions into metal NPs [33]. Similarly, other metal ions are converted to respective metal NPs as plant extracts are capable of forming NPs by adding metal salt to the solution. The color change in metal NPs varies from each other for example, dark brown, wine red, reddish-brown, and white color for silver, gold, iron, and zinc oxide NPs, respectively.

Nanoparticle Synthesis from Asteraceae Species
A large number of Asteraceae members have been utilized for the synthesis of various nanoparticles such as gold, silver, iron, copper, etc. For example, silver NPs synthesized from Asteraceae family members have significant catalytic action, atomic behavior, and biochemical reactivity due to large surface area. Recognition, reduction, limited nucleation, and growth help in the formation of silver NPs. In the recognition stage, the metal ions will be trapped on the surface protein of the plant extract by electrostatic interaction. Thereafter, proteins present in the extract reduce the Ag+ ions to Ag 0 by changing the secondary structure of the protein. This causes Ag ions reduction and accumulation in nuclei. The linkage of protein and a large number of biomolecules in the solution may lead to isotropic growth and the production of stable NPs [149].
The NPs synthesized by the addition of silver solution to the extract via. the green method is detected by color change. The color change is an indicator of the Ag ions reduction to Ag NPs by the plant extract phytochemicals. Briefly, the phytochemical compounds such as polyphenols, terpenoids, etc., present in the extract of Asteraceae members, donate electrons to reduce metal ions and form zero-valent metal atoms. Eventually, the collision of metal atoms with these atoms in the mixture results in the formation of several atoms with a stable core. These atoms will perform as nucleation regions and will form clusters that will continue to grow till an active supply of atoms, results in NPs formation. The process is carried out by the reduction of metal ions into metal NPs [33]. Similarly, other metal ions are converted to respective metal NPs as plant extracts are capable of forming NPs by adding metal salt to the solution. The color change in metal NPs varies from each other for example, dark brown, wine red, reddish-brown, and white color for silver, gold, iron, and zinc oxide NPs, respectively.

Factors Affecting the Synthesis of Asteraceae NPs
The green synthesis of metal nanoparticle formation is by metal ion reduction caused by phytochemical compounds present in Asteraceae members. Several factors affect the synthesis of NPs such as plant extract concentration, metal ions concentration, temperature, pH, and reaction time. These factors affect the size, shape, and distribution of NPs.

Temperature
During nanoparticle synthesis, temperature plays a crucial role in metal ion reduction to metal NPs. Normally, the reaction is carried out at room temperature, but it is also reported that some members of the Asteraceae family need a higher temperature to reduce the metal ions to metal NPs. Studies report silver NPs synthesized at room temperature (Acanthospermum hispidum and Anthemis atropatana), 40 • C (Achillea biebersteinii), 60 • C (Centratherum anthelmminticum), and 80 • C (Arnicae anthodium) [17,18,22,23,35]. UV-Vis spectroscopy explains that Ag NPs synthesized from leaves of Arctium lappa and Eupatorium odartum at 90 • C give an intense surface plasmon resonance (SPR) band and this intense SPR band indicates synthesis of NPs on a large scale [6,54]. At room temperature, gold NPs could be synthesized from Centaurea behens leaf extract when it is mixed with chloroauric acid [95]. Rectangular, cubic, and hexagonal-shaped Cu NPs can be synthesized using Ageratum houstonianum leaf extract at room temperature [13]. At 55 • C, a dark brown colored copper nanoparticle solution was formed from copper (II) nitrate trihydrate solution and aqueous leaf extract of Calendula officinalis [150]. In copper nanoparticle formation, when time increases the surface plasmon resonance decreases due to the oxidation of Cu NPs [151]. Metal oxide NPs such as iron oxide NPs and ZnO NPs were formed from Artemisia species and metal precursors at room temperature [114,127]. pH pH is a significant parameter during the synthesis of NPs. NPs' size, shape, and stability are affected by the reacting solutions' nature, i.e., acidic and alkaline medium. Reports suggest large-sized NPs are formed in an acidic medium and small-sized NPs are formed in an alkaline medium. However, the conversion efficiency of NPs is high in an alkaline medium [152]. Studies on the pH effect on AgNPs' formation using Tithonia diversifolia showed absorbance intensity increased gradually with an increase in pH range. However, in basic and neutral pH, the Ag NPs formation was very fast which was evident from the color change in the reaction mixture. However, at basic pH, there is a possibility of Ag ions precipitating as AgOH. Studies support pH 7 as the optimal pH to synthesize silver NPs [86]. pH was maintained at 5.4 to synthesize gold NPs from an aqueous extract of Sphaeranthus indicus and hydrogen tetrachloroaurate (II) trihydrate [153]. Different pH levels such as 9, 10, 11, and 12 were also used for the synthesis of zinc oxide NPs from Tragopogon collinus extract, and a broad peak was observed in pH 9 and a narrow peak showed in pH 12 solution. The broad peak could be due to the large particle size and the narrow peak due to the nanosized material. Therefore, pH 12 was concluded as best for zinc oxide NPs formation using Tragopogon collinus [125].

Reaction Time
Reaction time is a major factor in the synthesis of NPs. In Asteraceae-mediated nanoparticle synthesis, the formation of NPs takes place immediately after adding the metal precursor. Interestingly, the reduction and synthesis of silver NPs using Bidens frondosa extract were observed using UV-visible spectroscopic analysis. Silver nitrate solution addition to B. frondosa extract, Ag NPs synthesis started immediately and maximum production of AgNPs occurred at ambient temperature on 5 h of incubation [28]. The size, shape, and stability of the nanoparticle are also dependent upon the reaction time. The reaction time varies based on factors such as the concentration of metal ions, phytochemicals present, temperature, and pH of the plant extract [154]. Initially, the mixture of Sphaeranthus indicus extract and AuCl 4 solution was light yellow color, it changed to a wine-red color after 30 min of stirring [153].

Metal Ion Concentration
Metal ion concentration depends upon which metal is being used to synthesize NPs. Studies reported that for silver nanoparticle synthesis, the frequently used concentration is 1 mM, and other concentrations (1, 2, 3, 5, 8, 10, 53, 100, and 200 mM) of metal NPs are synthesized [148]. Varying concentrations of zinc acetate dihydrate (0.05 to 0.25 M) were taken to synthesize zinc oxide NPs from the mixture of zinc acetate dihydrate and aqueous extract of Tragopogon collinus. Results showed that the absorption intensity was low at 0.2 M and high at 0.05 M. When metal ion concentration is increased beyond the threshold then gradually the nanoparticle synthesis will be decreased, and also higher concentration can lead to the agglomeration of the NPs [125]. Metal ions concentration also varies based on the presence of phytochemicals. The concentration of metal ions will also affect the size, shape, and uses of NPs [148].

Plant Extract Concentration
Concentration of plant extract depends upon the number of phytochemicals present in the plant. The concentration of phytochemicals varies among plants and within plant families. Studies revealed that 0.1 g to 10 g of plant parts were utilized to synthesize NPs [128,133]. An amount of 10 g of Wedelia urticifolia leaves was utilized to synthesize magnetic iron oxide nanorods. Similar studies revealed that 20 g dried powder of Bidens pilosa, Galinsoga parviflora, and Conyza bonariensis was utilized to synthesize iron NPs [128]. Investigation of the production of zinc oxide nanoparticles using Tragopogon collinus, different amounts of extracts (0.25, 0.5, 1, and 2 mL) were utilized. The result showed that 1 ml of the extract van reduce 50 mL of 0.01 M of zinc acetate dihydrate solution, for the synthesis of a large quantity of zinc oxide NPs. The optimum quantity or higher amount of the extract increases the intensity of the absorbance peak. The quantity of synthesized NPs increases when the phytochemical present in the extract is more. Hence, large quantities of extract increase the production of NPs with improved absorption intensity [125].

Separation of NPs
The centrifugation approach for purifying NPs is frequently used to remove residual components and byproducts. Apart from centrifugation, NPs can be separated using chromatography and electrophoresis techniques [155]. Appropriate separation and purification are critical for nanoparticle characterization and applications. As noted in the reviewed publications, the green synthesis produced a variety of forms and sizes, the majority of which were spherical and polydisperse, and was proven to be efficient for the creation of silver NPs. Green synthesis, compared to physical and chemical synthesis processes results in less controlled morphologies, which may be related to several reducing/capping phytochemicals, which cause multiple redox reaction rates and growth of the NPs [16].

UV-Visible Spectroscopy
UV-Vis is a relatively easier technique that permits rapid identification and characterization of NPs. Because of the interaction of light with movable surface electrons of NPs produces a significant absorbance band in the 400-500 nm range known as surface plasmon resonance (SPR) [157].  [8,17,94,107,112,134,137,140,142,143].
The copper NPs synthesized using Achillea biebersteinii leaf aqueous extract peaked at 577 nm [107]. Iron NPs synthesized using Ageratum conyzoides extracts were observed at 390 nm [8]. Biosynthesized titanium dioxide NPs by using Echinacea purpurea Herba extract that showed a peak at 280 nm [138]. Gold NPs synthesized using flower extract of Carthamus tinctorius showed a peak at 560 nm [158].

Fourier Transforms Infrared Spectroscopy
The FT-IR reveals the surface properties of nanomaterials. This method aids in the identification of functional groups in both phytoconstituents and the resultant NPs. The FT-IR analysis of plant phytochemicals in free form or attached to NPs occasionally predicts minor band changes. There have been few studies on the use of pure phytochemical substances in the manufacture and use of NPs [45]. The list of nanoparticles synthesized from Asteraceae family, which characterized through FT-IR spectra described in Table 3.      [13]. The AuNPs peaks were observed at 415, 406, 394, 383, and 1629, which detect metal oxide bonds. The Cu NPs represent broad peaks at 3378 cm −1 and can be assigned to the phenolic compounds with OH bonds such as flavonoids, tannins, and glycoside derivatives. In addition, peaks at 1100 and 1700 cm −1 depict C-O and C=O stretching, respectively, of Blumea balsamifera leaf extracts [108]. The peaks 1264 and 1077 indicate the presence of C-O stretching of alcohols, carboxylic acids, and ester and ether groups in Pd NPs [112].

X-ray Diffraction
XRD offers chemical information for both elemental and phase research. XRD is beneficial for measuring stress and analysis of texture, in addition to chemical characterization. XRD analysis requires crystalline samples, however, the technique can determine the degree of crystallinity in polymers. XRD has typically been used for bulk sample analysis. However, with the introduction of new optical techniques, the thin-film examination may now be performed [160].
The XRD pattern of CuNPs was synthesized from Eclipta prostrata leaves extract, showing the formation of a face-centered cubic (FCC) arrangement ranging from 23 to 57 nm, with an average size of 31±1.2 nm [109]. Peaks for AgNPs were observed at 38

Zeta Potential
The zeta potential indicates a nanoparticle's charge concerning its surroundings. The zeta potential, however, is not a measurement of the molecule's surface charge; rather, it is a measurement of the electric double layer formed by the surrounding ions in the solution. Zeta potential between 10 and +10 mV are essentially considered neutral, but zeta potential greater than +30 mV or less than 30 mV are strong cations and strong anions, respectively [161].
The zeta potential of synthesized AgNPs from Centratherum anthalminticum (L.) Kuntze was measured at −25.75 mV [35]. The zeta potential was observed at −31 mV suggesting the stability of AgNPs synthesized from Artemisia marschalliana [24]. The superparamagnetic Fe 2 O 3 NPs synthesized using the Stevia plant showed a magnitude of zeta potential observed at −41.1 mV [131]. The AuNPs synthesized by Cichorium intybus L. showed a zeta potential of −19.7 eV. Zeta potential measurement was performed to predict the surface charge and stability of NPs [96].

Dynamic Light Scattering (DLS)
The sizing of NPs by DLS uses temporal variation of scattered light from suspended particles in Brownian motion to calculate their hydrodynamic size distribution [161,162]. It measures the hydrodynamic size, direct study of retention periods (also offers a hydrodynamic size), and differential refractometry or viscometry to assess macromolecular components' molecular weight. [163]. The particle size of copper NPs synthesized by using Ageratum houstonianum Mill leaf extract was observed to be approx. 80 nm. The size of dispersed NPs was also confirmed by DLS analysis [13]. AuNPs synthesized by Cichorium intybus L. and Elephantopus scaber (Linn.) leaf extract showed the particle size 1.7-3.2 nm and 20-40 nm, respectively [96].

Differential Scanning Calorimetry (DSC)
Melting characteristics and dependent melting temperature depression of synthesized nanomaterials are determined using DSC. The Gibbs-Thomson equation is utilized to study the size-dependent melting temperature property of alloy NPs, yielding a satisfactory prediction of melting temperature depression [163,164].

Thermogravimetric Analysis (TGA)
In a controlled environment, the change in mass of a sample as a function of temperature and/or time is measured by TGA. A high-precision thermobalance is coupled to a pan/crucible holder within a temperature-controlled furnace to form the thermogravimetric analyzer used for TGA studies. The sample environment is controlled by a purge gas supplied into the furnace, such as nitrogen gas for an inert atmosphere or air/oxygen for an oxidizing atmosphere. Temperatures ranging from room temperature to 1000 • C are ideal for TGA studies [165].
After heating to 900 • C, the biosynthesized Ag/AgCl NPs using aqueous leaf extract of Oedera genistifolia preserved more than 70% of their original weight. Initial weight loss between 30-200 • C might be attributed to Ag/AgCl NPs moisture loss, and subsequent weight loss was detected. At 900 • C, the Ag/AgCl NPs preserved around 70% of their weight, indicating their resilience [67]. TGA provides the measure of biosynthesized IONPs from Artemisia vulgaris leaf extract weight as temperature varies over time. At temperatures below 200 • C, the mass of NPs varies by about 100%, indicating that the substance is related to water. At temperatures of up to 200 • C, IONPs begin to lose mass, indicating the breakdown of NPs coated biomolecule compounds [127].

Selected Area Electron Diffraction (SAED)
SAED patterns were utilized to determine the typical morphological characteristics, framework, crystal structure, and chemical properties to identify the particles studied. For TiO 2 rutile nano-size granules, a series of field examinations were carried out at various time frames and weather conditions to demonstrate the preliminary capability of these collecting and analysis methods [166]. SAED pattern for AgNPs synthesized using Matricaria recutita (Babunah) plant extract confirmed a spot pattern with XRD peak values <311>, <220>, and <111> planes [65].

Scanning Electron Microscopy (SEM)
SEM pictures were captured in secondary electron mode (accelerating voltage of 10 kV) and processed with Image Tool software. The granule sizes were measured and compared to the Feret diameters. As metal sputtering sources, Pt/Pd and Cr targets (99.99% purity) were used, which create a configuration of distinct nanomaterials. A conducting sample of 6 m thick aluminum foil was used. Within the resolution range of the electron microscope utilized (1-3 nm), no NPs were found on its surface. Silica gel on chromatograms was used as a 2D nonconducting sample. Molecular sieves with well-developed 3D surface morphology were used as samples [167]. The investigation of NPs produced by magnet iron sputtering is also of interest to enhance experimental processes. SEM investigations of nonconducting materials are made more informative by the deposition of a metal onto a sample surface through magnetron sputtering [168].
The size and form of the Ag NPs produced from Eclipta alba leaf extract were measured, having a range of sizes from 310 to 400 nm [51]. The formation of AuNPs with Gundelia tournefortii L. possessed a spherical shape with an average diameter of 40-45 nm [102]. The Cu NPs size was confirmed to be 30-55 nm [108]. CuO NPs synthesized using Anthemis nobilis flowers show morphology-like rectangular structures ranging from 8-20 nm [135]. ZnO NPs synthesized using Artemisia aucheri are depicted as seabeds consisting of spherical and granular shapes in the range of 15-40 nm [169]. The nanoparticle sizes were observed in a range of 10 to 180 nm, 10 [24,51,114,137,145,159].

Transmission Electron Microscopy (TEM)
An electron beam imaging method for visualizing nanostructured samples that provide considerably higher resolution than light-based imaging techniques. Transmission electron microscopy is the best method for directly measuring nanoparticle size, grain boundaries, diameter, and morphological characteristics. The particle size range is wide, spanning from 1 nm to 5 nm. There is, however, a strong predilection for very tiny agglomeration. We divided them into four categories: FCC, icosahedral, decahedral, and twinned particles. It should be noted that our approach produces particles with an alkyl-thiol molecule passivating the surface [170].
The zinc oxide NPs synthesized using the Artemisia pallens plant extract showed a TEM result that shows a homogenous wurtzite structure [114]. The NiO NPs biosynthesized using Tagetes erecta L leaf extract revealed irregular forms of NPs [141]. The particle size ranges from 5 to 25 nm spherical particles for CuO NPs synthesized by Acanthospermum hispidum L. extract [134]. The spherical shape of AgNPs from Erigeron bonariensis with a particle size of 13 nm [53]. Gold NPs synthesized by Solidago canadensis L. extract showed a combination of single crystals and twinned particles [103]. The nanoparticle sizes were observed in a range of 10 to 100 nm, 10 to 50 nm, 20 to 50 nm, 5 to 50 nm, 20 to 70 nm, 5 to 60 nm, 12 to 50 nm, 5 to 50 nm, 8 to 20 nm, 5 to 25 nm for Ag, Au, Cu, Pd, ZnO, Fe 2 O 3 , CuO, TiO 2 , CO 3 O 4 , and MgO NPs, respectively [17,94,114,128,137,145,159].

Scanning Transmission Mode (STEM)
The STEM can approach atomic resolution, enabling direct imaging of smaller dimensions previously unobservable using traditional electron microscopy techniques. Combining this model with a high-angle annular dark-field detector, where the contrast on the picture is generally proportional to Z (where n is near 2), it is possible to identify elements on materials just solely on their atomic weight difference. This direct interpretation is of particular importance in the catalysis sector since bimetallic NPs are utilized in a variety of processes, including CO oxidation, hydrocarbon hydrogenation, and vinyl acetate production, among others. Probes as small as one can now be made, single molecules can be photographed, and the structure and form of microscopic NPs as small as a few nanometers may be detected [171]. The silver NPs synthesized using Ambrosia arborescens were observed as spherical and dispersed in solution with an average particle size of 14 ± 6 nm [21].

Application of Asteraceae-Based Nanoparticles
Unlike the traditional application of plants from the Asteraceae family, green synthesized nanoparticles have shown highly significant biological responses. These may be attributed to the small size of these particles which can be targeted specifically for biological applications such as antimicrobial, anticancer, photocatalytic, etc. (Figures 1 and 3, Tables 1 and 2).

Antimicrobial Activity
Researchers have reported numerous antimicrobial activities by green synthesized NPs using Asteraceae members. NPs such as silver, copper, gold, iron oxide, zinc oxide, titanium oxide, nickel oxide, and copper oxides synthesized from different members of Asteraceae exhibited great antimicrobial activity. Most commonly, Ag NPs are synthesized from Asteraceae members as Ag is a safe non-toxic metal. Ag NPs have great potential because of their antimicrobial properties and were also used in the treatment of contaminated groundwater. Ag NPs are good antibiotics and preservatives [172], thus used in the food industry. The Ag NPs synthesized from Carthamus tinctorius showed antibacterial activity against toxic pathogens such as Pseudomonas fluorescens (ATCC 13867) and Staphylococcus aureus (ATCC 25923) in the food industry [33]. Ag NPs synthesized from leaf extract of Eupatorium odaratum exhibited a broad spectrum of antibacterial and antifungal potential against Escherichia coli, Bacillus subtilis, S. aureus, Salmonella typhi, and Candida albicans, respectively [54]. Leaves of Tagetes erecta were capable of synthesizing Ag NPs and showed antibacterial activity against E. coli (DH5-Alpha) and Staphylococcus aureus (ATCC9144™) [173]. Quasi-spherical shaped Ag NPs synthesized from Acanthospermum hispidum have antibacterial, antifungal, and antimycobacterial activity [17].

Application of Asteraceae-Based Nanoparticles
Unlike the traditional application of plants from the Asteraceae family, green synthesized nanoparticles have shown highly significant biological responses. These may be attributed to the small size of these particles which can be targeted specifically for biological applications such as antimicrobial, anticancer, photocatalytic, etc. (Figures 1 and 3, Tables 1 and 2).

Antioxidant Activity
Antioxidants are substances that may remove, prevent, or delay cell damage caused by free radicals including reactive oxygen species (ROS), reactive nitrogen species (RNS), and other unstable molecules. DPPH (2,2-diphenyl-1-picryl-hydrazyl) assay is a commonly used method for the determination of antioxidant capacity [175]. Many researchers report that Asteraceae-mediated NPs have high antioxidant activity and can be used to treat diseases caused by oxidative stress and free radical-related disease. High antioxidant properties of Asteraceae members are accounted for by a large amount of phenolic and flavonoid content.
Studies report that synthesized Ag NPs from the leaf extract of Ageratum conyzoides has high antioxidant properties [13]. Ag NPs synthesized from Calendula officinalis are a good source of antioxidants because of their high antioxidant activity and can be used in the production of medicines and cosmetics [176]. Recent research proved that Au NPs synthesized from leaves of Centaurea behen, Crassocephalum rubens, Gundelia tournefortii, and seeds of Cichorium intybus can act as antioxidants [43,95,102]. Antioxidants were also produced from ZnO NPs synthesized from the flower of Tagetes erecta and seeds of Zinnia elegans [93,123]. Aqueous extract of Silybum marianum synthesized ZnO NPs showed antioxidant properties [122]. Cu NPs synthesized from Blumea balsamifera, and Eclipta prostrata, also showed antioxidant activities [108,109].

Anticancer Activity
NPs synthesized from the Asteraceae family have a higher potential for controlling the growth and multiplication of tumor cells. Ag NPs synthesized from Artemisia marschalliana and A. turcomanica exhibit anticancer activity in the human gastric cancer AGS cell line [24,25]. ZnO NPs from Achillea millefolium are highly stable and biocompatible. They showed cytotoxic activity on lung and colon cancer cells [177]. ZnO NPs from leaf extract of Costus pictus have cytotoxic activity against Dalton lymphoma ascites cells [9]. Au NPs from leaf extract of Centaurea behen showed anticancer activity against leukemia cell line [95]. ZnO NPs using leaf extract of Cynara scolymus were found to possess anti-proliferative activity against the human breast cancer cell line [116].

Antidiabetic Activity
Diabetes is a metabolic disorder that is developed due to glucose intolerance and hyperglycemia. It is also caused due to changes in food and lifestyle. A recent investigation reported that silver NPs synthesized from Phagnalon niveum methanol extract demonstrated antidiabetic activity by reducing the blood glucose level and also reduced the body weight of rats in 1 to 21 days [178]. Spherical shaped-CuO NPs synthesized from Silybum marianum seed extract displayed great enzymatic inhibitory activity against ureases, alpha-amylase, and lipases so it was concluded that they can act as antidiabetic agents [179]. ZnO NPs and Au NPs which are synthesized using Dicoma anomala and Eclipta alba, respectively, are good alternative sources for antidiabetic medicine [98,117].

Antileishmanial Activity
Leishmania is a parasitic protozoan that is a causative organism for oropharyngeal mucosa inflammation, cutaneous lesions, and visceral infections. Antileishmanial drugs are usually antimonial compounds, they are highly toxic. Pentavalent antimony drugs such as meglumine antimoniate and sodium stibogluconate are used in the initial treatment of leishmaniasis [180]. A recent study in green synthesis proved that zinc oxide NPs synthesized using Silybum marianum can replace toxic antimonial drugs to destroy Leishmania tropica (KMH23) which causes Leishmaniasis [122].

Anti-Angiogenic Activity
Angiogenesis has a major role in atherosclerosis, tumor growth, myocardial infarction, carcinogenesis, limb ischemia, and cardiac ischemia. Recent studies report Ag NPs synthesized from flower extract of Achillea biebersteinii can reduce angiogenesis. The antiangiogenic activity of the silver nanoparticle was studied in the rat aortic ring model [18].

Photocatalytic Activity
Nanoparticles have been utilized for the degradation of various anionic, catatonic, and neutral dyes [181]. Dyes, commonly used in paper, plastic, food, cosmetics, leather, textile, and pharmaceutical industries and have proven to be harmful to both aquatic and human life due to their toxic, mutagenic, carcinogenic, and teratogenic effects. Research supports NPs synthesized from Asteraceae members as good catalysts to degrade the toxic dyes to non-toxic compounds. Ag NPs synthesized from leaf extract of Ageratum conyzoides showed photocatalytic degradation properties [13]. ZnO NPs formed from Cynara scolymus leaf extract were able to degrade 94.3% of methyl violet and 89.5% of malachite green dyes after 120 min of UV exposure [116]. A total of 83% of methylene blue was degraded by NiO NPs synthesized from leaf extract of Ageratum conyzoides [140]. Under solar light, TiO 2 NPs synthesized from leaf extract of Ageratina altissima had the potential to degrade dyes such as crystal violet, methylene blue, alizarin red, and methyl orange [137]. FeO NPs synthesized from Wedelia urticifolia leaf extract and Centaurea cyanus, showed photocatalytic degradation activity and were used for the removal of toxic chemicals or dyes from the aquatic environment [129,133].

Other Activities
Nanoparticles synthesized from plants of the Asteraceae family revealed other applications such as anti-efflux activity, DNA binding, detection of mercury ions, cutaneous wound healing effect, electrochemical sensing activity, hydrogen peroxide detection, and tyrosinase inhibitory activity. Silver NPs synthesized from Acroptilon repens have been shown to have anti-efflux activity against clinical isolates such as Acinetobacter bumanni [19,129]. DNA binding and Hydrogen peroxide sensing properties have been found in Agertum conyzoides Ag NPs [13]. Ag NPs formed by the reduction of Bidens frondosa and Ag salt precursor showed tyrosinase inhibitory activity [28]. NiO NPs from the leaf extracts of Tagetes erecta have electrochemical sensing properties [141]. Au and Ag NPs synthesized from Gundelia tournefortii showed cutaneous wound healing activity [57,102] and Ag NPs synthesized from Dahlia pinnata were utilized for mercury ion detection [46].

Toxicity of Asteraceae Mediated Nanoparticles
NPs are highly toxic to the cells in comparison to large particles of the same chemicals. Studies concluded that the toxicity of NPs is inversely proportional to the size of the particles [182]. Several studies with the NPs synthesized from Asteraceae members have looked into how this toxicity can be used as an application to better suit the environment. Even with their toxicity to humans, low levels of NPs can still be used with an apt efficiency rate to reduce pollution as well as kill out several harmful living agents within our environment [183].
Ag NPs synthesized from the flower extracts of Chrysanthemum indicum have been proven to have lethal activity. These NPs can bring about the maximum mortality rate of Anopheles stephensi mosquitoes regardless of whether it is larvae or pupae [184].
The Cd NPs synthesized from Tagetes sp. showed a similar type of maximum mortality rate against Aedes albopictus at 72 h incubation while normal incubation only yielded 65 to 70% mortality. This showed that not only concentration but also incubation time can affect the toxicity that NPs have on particular mosquitos or other organisms. So, the ideal way to use NPs would be to use less concentration with high incubation time [185]. The leaf extract of Ambrosia arborescens and subsequent Ag NPs produced from the same plant extracts NPs had a dose-dependent toxic effect against Aedes aegypti larvae. However, no mortality rate was observed in the control groups [21]. Gold NPs from Sphaeranthus indicus extract did not have any particular toxic effect on the plant cells or aquatic invertebrates such as Artemia nupulii when tested with a particular similar dose-dependent concentration. However, it was shown to prompt the mitotic division of the root tip cells in Allium cepa, and also promoted the germination of pollen grains in Gloriosa superba [153].
While in the case of humans, toxicity is a bit different compared to the other fauna that has been characterized. NPs of size below 10 nm behave the same as gases, so they can easily enter through human tissue. After inhalation, NPs spread to the heart, lungs, spleen, liver, brain, and gastrointestinal tract and may disrupt the function of normal cells [182].

Constraints of Asteraceae-Mediated Nanoparticle Synthesis
Asteraceae-mediated nanoparticles have significant activities and applications, however, there are limitations in plant selection, synthesis process, nanoparticle quality assurances, and their applications. These limitations challenge the production of nanoparticles in large-scale and industrial production. Several plants in the Asteraceae family have been used to synthesize locally available nanoparticles. Yet, industrial production of Asteraceae-mediated nanoparticles is very hard to achieve due to the varying effects of climatic conditions, growing seasons, and large-scale cultivation of plants used for synthesis. Some of the very important concerns in the process of synthesis are long reaction time, pH, temperature, the use of chemicals, and excessive energy consumption. The challenge in the separation and purification of nanoparticles due to the interference of other phytochemicals in plants is another obstacle faced during the process of synthesis. The quality of obtained nanoparticles could be affected due to agglomeration, irregular shape, size, and low yield. Another limitation of Asteraceae-mediated nanoparticles is in their application, the efficiency of activities will be low, and time-consuming and large amounts of nanoparticles should be utilized for the same to achieve activities more efficiently.

Conclusions and Prospects
Extracts from plant parts such as leaves, roots, flowers, peels, stems, bark, and biological modifications were effectively employed for the synthesis of NPs under ambient circumstances under extremely moderate reaction conditions due to the clear potential efficacy and eco-friendliness of biogenic synthesis. UV-Vis, SEM, TEM, HR-TEM, STEM, SAED, XRD, EDAX, DT-TGA, FTIR, TGA, DSC, and DLS techniques, etc., were utilized for characterization. Biogenic NPs have shown remarkable anti-cancer, anti-diabetic, antibacterial, antifungal, and antioxidant properties. Under different temperature and pH conditions, the NPs remained stable for a longer amount of time. Phytochemicals in the plant extracts, such as polyphenols, polyphenolics, flavonoids, and other functional groups, different nanomaterial frameworks, and morphological characteristics were formed. Asteraceae is a large family with a vast number of beneficial plants. Silver, gold, copper, iron oxide, and zinc oxide NPs are successfully synthesized using Asteraceae members. NPs synthesized using Asteraceae members have huge applications such as antibacterial, antifungal, antiparasitic, antioxidant, photocatalytic degradation, and cytotoxic activities and thus need significant attention to be an important area of research in phyto-nanotechnology that provides new avenues towards the eco-friendly and economical synthesis of nanostructured materials. The mechanism involved in the synthesis of NPs, which is briefly through phytochemicals present in plants, aids in the reduction of metal NPs, but the exact mechanism remains unknown as to which phytochemicals play an important role in synthesis. It is said that collectively bioactive compounds aid in synthesis. It would be fascinating to learn which phytochemical molecule is responsible for green nanoparticle production.

Data Availability Statement:
The data presented in this study are available on request from the corresponding authors.