Recent Advancements in Plant-Derived Nanomaterials Research for Biomedical Applications

Engineering, physics, chemistry, and biology are all involved in nanotechnology, which comprises a wide variety of multidisciplinary scientific field devices. The holistic utilization of metallic nanoparticles in the disciplines of bio-engineering and bio-medicine has attracted a great deal of attention. Medical nanotechnology research can offer immense health benefits for humans. While the advantages of developing nanomaterials have been well documented, it is precisely apparent that there are still some major issues that remain unattended to those need to be resolved immediately so as to ensure that they do not adversely affect living organisms in any manner. The existence of nanoparticles gives them particular value in biology and materials science, as an emerging scientific field, with multiple applications in science and technology, especially with numerous frontiers in the development of new materials. Presented here is a review of recent noteworthy developments regarding plant-derived nanomaterials and their use in the development of medicine and biomedical applications around the world.


Introduction to Nanoparticles
Nanomaterials have brought a revolution in the area of biomedical research due to having a high loading capacity and strong protection to the payloads. Nanoparticles (NP) have a variety of choices in biomedicine, bio-labeling, agriculture, antimicrobial agents, and in many other areas [1]. As a result of their wide range of applications in a variety of fields, nanoparticles have become a hot topic of study in recent years, including in diagnostics, biomarkers, cell identification, antimicrobials, drug delivery, and cancer therapies [2]. Physical, chemical, and biological methods can all be used to synthesize and develop nanoparticles. However, biological methods are regarded to be an especially appealing medicine, and diagnostics. Various anticancerous and antimicrobial properties of NPs are shown in Figure 1.  4 ·3H2O, H 2 PtCl 2 ) after treatment with bioreducing agents (flavonoids, amino acids, heterocyclic compounds, phenolics, polyphenols, saponins, etc.) form stable nanoparticles. These nanoparticles (Ag-NPs), when treated on cancerous cells, activates the Caspase-3 pathway, which subsequently activates the different cellular process such as ROS generation, accumulation of autophagolysomes, ER stress generated, LDH releases, and mitochondria disrupted, and eventually leads to cell collapse, hence cell death. The NPs degrade the peptidoglycan layer of bacterial cell wall. These NPs disturb the electron transport chain (ETC), which eventually leads to reactive oxygen species (ROS) generation. They intercalate with the protein and leading to its denaturation. Furthermore, NPs also create nicks in the plasmid. All these events inside the bacterial cell lead to its death.

Different Types of Nanoparticles
Type of nanoparticles varies with the process by which nanoparticles are synthesized, as shown in the Figure 2. Nanoparticles synthesised from plants presents a preferable source of NP synthesis. The synthesis of NPs from plants has many advantages over physical and chemical modes of synthesis. It is more straightforward, rapid, and cost effective than chemical or physical nanoparticles synthesis and uses less energy and takes place under moderate operating conditions. Almost all parts of the plant, including the root, stem, latex, leaf, and bark, can be used for the synthesis of NPs. Although the exact mechanism to synthesize NPs from plants is ambiguous, still, it has been found that phenols, flavanoids and many more biomolecules present in plants can help in the reduction of metal ions resulting in the synthesis of NPs. Due to their abundance of capabilities and bioactive reducing metabolites in many forms, the biological synthesis of nanomaterials, in particular silver nanoparticles, has received a significant amount of attention. 2.1. Metallic Nanoparticles 2.1.1. Silver Nanoparticles Simple, green, and natural ways of synthesizing silver nanoparticles out of AgNO 3 have been discovered from plant parts. Silver nanoparticles are produced in an ecofriendly and straightforward way, so they can be used effectively as nanomedicines in a wide variety of human ailments [19]. In addition to having some environment-damaging effects, human health, and more importantly, normal cells, using chemical methods for synthesizing AgNPs presents some inherent disadvantages. Electrostatic attraction and affinity with sulfur proteins cause silver ions to adhere to cellular walls and cytoplasmic membranes, resulting in the disruption of bacterial envelopes by increasing cytoplasmic membrane permeability. For the synthesis of silver NPs, researchers investigated the potential of walnut green husk. Walnut green husk extracted into aqueous solution and used as both a reducing and stabilizing agent and synthesized NPs have been further investigated for their anticancer, antioxidant, and antimicrobial properties [20]. The silver nanoparticles can affect bacterial signal transduction by affecting the phosphorylation of protein substrates and can interfere with tyrosine phosphorylation. Signal transduction disruption leads to apoptosis and multiplication termination of the cell [21]. In a study by Radzig and colleagues, GNPs stabilized with hydrolyzed case in peptides significantly reduced the growth and the biomass of Gram-negative bacteria [22]. There are several mechanisms associated with reactive oxygen species (ROS) production in nanoparticles, and it has been suggested that nano-silver toxicity may be a result of ROS, such as with free radicals, produced by oxidative damage [23,24]. Implementing a structured delivery system can enhance the effects of AgNPs, which have antimicrobial activity as well in addition to have antimicrobial and antiretroviral effects [25][26][27][28][29]. Doxorubicin (DOX), a hydrophilic antitumor drug, combined with AgNPs can significantly decrease the growth and proliferation of tumor cell and is thus much more effective than either DOX or AgNPs on their own [30]. Moreover, an adherent silver nanoparticle releases high concentrations of silver ions on a bacteria's surface and chemically binds with the bacterial surface, leading to its membrane destruction [31].

Gold Nanoparticles
The application of colloidal gold solutions to cure specific infections also dates back thousands of years. Since gold is among the most biocompatible metals, as well as possesses a variety of beneficial properties, the need for well-engineered AuNPs is growing on account of their unique properties such as being life-compatible, providing a higher surface reactivity, being quite small, having varied shapes, and resisting oxidation readily. For the synthesis of gold NPs, methods used by researchers include the reduction of gold (III) derivatives. One of the gold reduction methods used by the Daniel and Astruc., 2004, for the synthesis of gold NPs was reducing HAuCl4 with citrate in water leading to synthesis of gold NPs [32]. It has been found that the fruit extracts containing organic constituents that are water soluble act as the principal reducing and capping agents, thereby reducing gold ions and forming AuNPs [33,34]. Antimicrobial properties are contributed by these NPs [35]. There are numerous biomedical applications for AuNPs due to their ability to be biosynthesized from plant extracts by reducing gold salt and thus having broad-range applications in biomedicines [36].

Copper Nanoparticles
Copper compounds are used to protect crops from a wide range of microbes and fungi, such as pathogens that cause infections by bacteria and fungi, due to their low cost, high protective activity, and low risk of resistance development [37]. Copper nanoparticles have excellent mending properties and are therefore added to lubricating oils as additives to reduce friction or restore worn surfaces [38]. In addition to substituting essential ions and blocking functional groups of proteins, copper is reported to be able to produce hydroperoxide free radicals, inactivate vital enzymes, and modify membrane integrity, thereby working as an antimicrobial agent [39,40]. Some fundamental properties of the antioxidant molecules, such as absorbing, neutralizing, or quenching the singlet and triplet oxygen activate the antioxidant system of CuNPs. For the synthesis of copper NPs, copper acetate tetrahydrate was used. A magnetic stirrer was used to dissolve copper acetate tetrahydrate and aqueous plant extract. The solution was boiled resulting in a green-colored paste, which was further heated in a furnace. After heating, black-colored powdered copper NPs were collected. Phytochemicals present on the surface of CuNPs result in the highest antioxidant activity because they contain a variety of bioreductive groups [41,42].

Platinum Nanoparticles (PtNPs)
The large surface areas of platinum nanoparticles (PtNPs) and their alloys make them excellent catalytic materials, and they can be used to reduce pollutants and trigger chemical reactions that facilitate the manufacture of chemicals of various kinds [43]. In addition to confirming the efficacy of nanomaterials, PtNPs have significant potential in the medical field. PtNPs in conjunction with low concentrations of anticancer drugs may provide synergistic anticancer activity/tumor reduction, but new strategies are still needed to investigate the subject. Platinum NPs were synthesized by grinding plant parts to make plant extract. This plant extract then added in H 2 PtCL 5 and put on constant magnetic stirring. Further, this solution was centrifuged, and platinum NPs were collected [44]. Research conducted by Kim et al., 2008 [45] demonstrates the antioxidant properties of platinum nanoparticles as well as their ability to mimic superoxide dismutase (SOD) and their anti-aging properties in Caenorhabditis elegans. Furthermore, the use of PtNPs as oxidative stress-related diseases therapies has been demonstrated in a study in which the addition of PtNPs to hydrogen-dissolved water inhibited tongue carcinoma cells HSC-4 [46].

Metal Oxide Nanoparticles (MO-NPs)
The metallic oxides have physiochemical qualities with a broad range of applications in research work and electronics [47,48]. In the past decades, metal oxide nanoparticles (MO-NPs) have been broadly used in biomedical applications. MO-NPs are of various types, viz., iron oxide (Fe 3 O 4 ), copper oxide (CuO), titanium oxide (TiO 2 ), and zinc oxide (ZnO). These MO-NPs have a wide range of applications from medical to environmental aspects; they act as a catalyst that can reduce or eliminate toxic impurities or hazardous material present in the environment [49,50]. These MO-NPs are usually seen as impervious to the environment and humans [51][52][53]. MO-NPs damage the bacteria's protein and DNA by inducing oxidative stress for the generation of ROS [54].

Zinc Oxide Nanoparticles (ZnO-NPs)
The characteristics of ZnO-NPs lie in their nano size and surface area-to-volume ratio, and personal peculiar biological properties, and they have been recognized and registered as a 'Safe material' [55,56]. A study conducted by [57] shows ZnO-NPs anticancer activity against liver cancer cell line HepG2 with an elevated level of genotoxicity and cytotoxicity associated with cell death/apoptosis. ZnO-NPs (spherical, 96-115 nm size) also exhibit remarkable anti-inflammatory properties with a 66.78 µg/mL IC50 value [58]. The ZnO-NPs have their application in the bioimaging field; they have blue emission and near UV emission spectra with yellow or green luminescence towards oxygen vacancy presence [59][60][61]. Research reported by Hameed et al., 2019 showed that a combination of NPs (Ag-ZnO-NPs) probably gradually shows greater antimicrobial activity than ZnO-NPs [62]. Probably the most prevalent form of zinc nanoparticles is zinc oxide; this NPs is commonly used in plastic, glass, ceramics, cement, rubber, food supplements, and non-flammable materials due to its wide range of compatible properties, which is also related to its convenient availability and low price [63]. In addition, zinc nanoparticles are both antimicrobial and antibacterial, and are UV-blocking as well, which allows them to be added into fabrics to provide a variety of functions, such as ultraviolet and visible light protection, antibacterial properties, and deodorant functions [64]. In many zinc nanoparticles, fluorescent properties are possible if these NPs can be modified, including ZinS and ZinSe, or quantum dots CdSe/ZnS, and that is why they are being considered for use in the future. According to a research study, zinc oxide nanoparticles are the most toxic to microbes of all metal oxide nanoparticles that have been examined in vitro for potential toxicity against salmonella typhi and staphylococcus aureus [65]. Moreover, ZnO nanoparticles have drawn tremendous attention as a low-cost and low-toxicity nanomaterial, with applications in cancer therapy, anti-bacterial properties, anti-inflammatory activities, anti-diabetic properties, and drug delivery [59,66]. Zinc oxide NPs were synthesized with plant leaf extract by zinc acetate dihydrate. Firstly, zinc acetate dihydrate was added in distilled water and put into constant stirring, and then aqueous leaf extract was introduced in its solution. After stirring, light yellow-white precipitate was collected and washed with distilled water many times. After distilled water washing, an ethanol wash was performed to remove impurities and the result was precipitate dried in a vacuum to get zinc oxide NPs [67].

Copper Oxide Nanoparticles (CuO-NPs)
The unique chemical, physical, electrical, thermal, and biological properties of CuO-NPs have given them an increased interest as nanomaterials. Copper NPs were synthesized with the help of Cu(CH 2 COO) 2 ·H 2 O. Cu(CH 2 COO) 2 ·H 2 O was dissolved in distilled water under constant stirring. Plant leaf extract then added in this solution and mixture gains stirred for a few hours. The prepared NPs were centrifuged, collected, and dried in an oven [68,69]. Playing a chief role in solar cells, catalysis, lithium-ion battery, and antimicrobial drugs, CuO-NPs are substantial, durable, and, compared to other organic and inorganic materials because they ensure a long shelf life [59,60,70,71]. Compared with plant extracts, the CuO-NPs are more sensitive to bacterial strains and are lethal due to subsequent interactions with DNA molecules, which cause disorder in structures by cross linking between nucleic acids. CuO-NPs are even good antioxidant agents compared to plant extracts [72].

Iron Oxide Nanoparticles (Fe 3 O 4 -NPs)
Iron Oxide NPs are considered incredibly stellar, biocompatible, and propitious and possess magnetic attributes that make them suitable for treating various diseases and infections [73,74]. A study reported by Chauhan and Upadhyay, 2019 [75] shows that iron oxide NPs were functionalized by coated with L-tyrosine, which gives a significant result against both the pathogenic bacterial strains Staphylococcus typhimurium and Staphylococcus aureus. Iron oxide NPs were synthesized by dissolving henna extract into ferrous sulfate salt solution. Ferrous sulphate was reduced by henna extract and washed with salt solution at constant stirring. The solution turned black, indicating the formation of iron oxide NPs. The solution was cooled and centrifuged to collect pellets. Obtained pellets were washed with distilled water and methanol to remove henna extract impurities and dried overnight to obtain iron oxide NPs. The iron oxide NPs are clinically approved and used as a delegate for magnetic NPs hyperthermia (cancer therapy, to raise the local temperature around the tumor to animate or kill cancer cells) [76]. Fe 3 O 4 -NPs as nanomedicine from plant extract (Euphorbia) show prominent antimicrobial activity against Aspergillus niger, Aspergillus fumigatus, and Arthogrophis cuboidal [77] 2.1.9. Titanium Oxide Nanoparticles (TiO 2 -NPs) TiO 2 -NPs have marvelous morphology, surface chemistry, optical properties, and biocompatibility [78]. They have a wide range of biomedical applications such as in disease diagnosis, surgical tools, bioimaging [79], tissue engineering, drug delivery, and also the synthesis of textiles, cosmetics, plastics, and foodstuffs [80,81]. TiO 2 -NPs are effective against various infectious microorganisms such as bacterial strains, protozoans, algae, viruses, prions, and microbial toxins [82]. TiO 2 -NPs are used as a nanocarrier (drug delivery) against the MDR breast cancer cells [83]. The green synthesized TiO 2 -NPs are also found effective against many larvicidal species of parasites such as Catharanthus [84], Calotropis gigantic (L.) [85], Solanum trilobatum L. [86], and Aspergillus niger [87]. The plantderived synthesis of titanium oxide NPs was achieved by mixing TiO2 with plant extract and incubation at room temperature for 24 h. Green-colored titanium oxide NPs were formed and were collected for further use [88].

Biomedical Applications of Various Plants-Derived NPs
By reformulating drugs with smaller particle sizes, nanotechnology can boost their oral bioavailability to a greater extent; thus, nanotechnology can replace many conventional oral formulations that are ineffective because they have poor bioavailability as a therapeutic option [89,90]. NPs are a promising option for synthetic chemical fungicides, since they provide a more eco-friendly alternative that enhances drug delivery, slowly releases active ingredients, and allows for lower doses of the active ingredient. In addition to being safer and more comfortable for patients, novel drug delivery systems would improve pharmacokinetics for easily degraded peptides and proteins that quickly degrade in the body and decrease the toxicological effects of drugs. Recent studies reported that grape exosome-like nanoparticles administered via oral administration to mice led to cells proliferating in the epithelium of the intestine and caused intestinal stem cells to proliferate. The natural and nontoxic delivery system might therefore be plant-derived edibles composed of nanoparticles characterized by its natural targeting of colonic tissues and anti-inflammatory properties. This system can be used for the treating of digestive tract diseases such as intestinal bowel disease (IBD) [91]. Furthermore, the study of NPs in leukocytes, in order to determine its specific role in gut inflammation, has shown that they inhibit Cyclin D1, a molecule that regulates cell cycle. In another study, it was found that in low concentrations, metal oxide nanoparticles have significant antimicrobial activity, and in comparison, with their bulk counterparts, they are low or non-toxic to humans [92]. The growing demand for green chemistry and nanotechnology has pushed for the development of green synthetic methods for the production of nanomaterials using plants, microbes, and other natural resources. Catalysis, medicine, cosmetics, agriculture, food packaging, water treatment, dye degradation, textile engineering, bioengineering sciences, sensors, imaging, biotechnology, electronics, optics, and other biological sectors are just some of the potential applications of these green plant-based NPs [93]. The type and biomedical application of various NPs derived from different kinds of plants are shown in Table 1. 8.

Yellowishbrown Liquid
Synthesized NPs were tested against osteosarcoma cells (MG- 63) in vitro and showed promising results against bone cancer cell lines. [105] 9.

Yellowishbrown Liquid
(i) Synthesized Ag-NPs effectively controlled autoantigen production that occurs during the inflammation process. (ii) Biosynthesized AgNPs impart potent cytotoxicity against the HeLa (cervical cancer) cell line. [106]

Red wine colour Liquid
Ag-NPs of belladone shows the potential halting of BSA protein denauturation. Mainly atropine and apoatropine were major antiinflammatory agents/compounds present in it. [2] 10. Gray color Solid ppt.

Dark brownish color
Liquid It exhibits antifungal activity in Candida tropicalis and Candida kefir fungal species. [110]

Dark brown color Liquid
These Ag-NPs exhibited antibacterial against Candida albicans, Candida kefyr Candida tropicalis, Aspergillus niger,and Aspergillus flavus and had fungicidal activity. Theyalso show good wound healing activity and can be used in the field of medicine.

Dark brown Liquid
It highly inhibited DENV-2 replication in vitro conditions with a viral inhibition percentage >90. [112]

Brown color Liquid
Its NPs are sensitive against the G + and G − bacterial sp. The highest zone of inhibition in the case of G + bacteria is towards Streptococcus Mutants,while in the case of G − bacteria, it is towards Escherichia coli. [72]

Black color Liquid
It shows antibacterial activity and maximum inhibition against Streptococcus mutans (G + ) bacterium, while in case of G − bacterium it shows maximum inhibition against Pseudomonas aeruginosa. [72]

Nanomedicine as Promising Anticancer Agent
In carrying anticancer agents, nanoparticles are primarily advantageous because of their ability to deliver anticancer agents to the tumor, tumor imaging, the storage of thousands of molecules of drugs, and resistance to solubility, stability, and stability issues [120]. In a study, AuNPs are found to have anticancerous activity against many cell lines such as the K-562 cell line, Hela cell line, MDA-MB cell line, and A-549 cell line, but surprisingly there was no effect of these AuNPs seen against the Vero cell line [121]. The ZnO nanoparticles present some cytotoxicity in cancer cells primarily through the increased release of dissolved zinc ions inside the cell, with enhanced ROS production leading to apoptotic cell death [122]. In a study, [123] fabricated ZnO nanoparticles were used for an anticancer evaluation using a chemical precipitation method. They demonstrated that differently sized ZnO nanoparticles inhibited fibrosarcoma HT1080 cell proliferation. In a study, the potential mechanism of TiO 2 (titanium dioxide) nanoformulations inhibiting cell proliferation was demonstrated. Studies have shown that TiO 2 can disrupt the cell cycle by blocking a number of DNA checkpoints during cell division [124]. Other than their studies in tumor microenvironments, TiO2-NPs have been involved in the redox homeostasis, neurodegeneration pathways, and NAD salvage mechanisms [125]. According to many recent studies, it was found that pure Au-TiO 2 -NPs, Zn-TiO 2 -NPs, and Ag-TiO 2 -NPs are capable of becoming genotoxic drugs when used as nanomedicines or chemotherapeutic drugs to treat cancer. Additionally, the radioactive probes can be used to penetrate deep into cancer tissues to treat them more effectively [126,127]. According to a study, nanomedicine must be goes through five steps to reach tumor cells including circulation, accumulation, penetration, and internalization followed by release [128].

Plant-Derived Nanofibers and Their Role in Wound Healing
Nanofibers have characteristic features such as a porous structure, exquisite interconnectivity between pores (desirable for wound healing), moisture availability, oxygen permeability, and the inhibitory effect against the microorganisms from outside; they have compliance to the skin at the wound site and have an awful property to slacken skin scars [148][149][150]. Many natural biopolymers such as polysaccharides (cellulose, starch, chitin, and chitosan), proteins (gelatin, keratin, fibrin, silk fibroin, and zein), proteoglycans, bacterial and algal polysaccharides, plant gums, and bioactive compounds (phytochemical constituents) have been at the center of attraction in the biomedical field. These natural plant-derived biopolymers have played a significant role in wound dressing and been successfully exploited for the formation of nanofibers through electrospinning. They show biocompatibility with materials required for wound healing due to similarity with human macromolecules, having properties such as biodegradability, a hemostatic nature, and non-toxicity [151][152][153][154][155]. Electrospun nanofibrous wound dressings materials loaded with synthetic antibiotics and nanoparticles have a detrimental effect on the environment and human health. Nanoparticles-loaded with phytochemicals have fewer side effects, are readily available, and are less costly [156]. A variety of natural biomolecules or compounds are selected for the nanoparticles. These nanoparticles are then converted into a nanofiber form that efficiently helps in wound dressing. The process of nanofiber formation and wound healing is illustrated in Figure 4. Curcuma longa L is the first plant extract loaded with ultra-fine cellulose acetate fiber mats and was manufactured by electrospinning [157]. The active component of Curcuma longa L is curcumin, which possesses a significant range of biological activities such as antibacterial, anti-inflammatory, antimicrobial, antioxidant, angiogenic effect, and anticancerous properties [158].

Plant-Derived Nanostructure Biomaterial and Their Role in Bone Regeneration
The process of bone regeneration occurs synergistically; a small defect in bone leads to the action of different cells, i.e., mesenchymal cells, osteogenic cells, and the cells of the immune system. Under the process of self-repaired bone leads to some physio-chemical and mechanical properties to tautologize the replaced bone [159]. Plant polyphenols show a promising role in tissue regeneration, as the process of remodeling is exacting a sophisticated process for the development of bone tissue regeneration. Due to natural antimicrobial and antioxidant activity, polyphenol acts as a potential drug in the modern biomedicine world. Polyphenols also have numerous bioactive compounds, micronutrients that maintain and protect bone health [160,161]. Electrospinning is widely used techniques that can produce nano-pore size and nano-diameters of plant-derived polyphenols with the fabrication of nano-fibrous scaffolds, as shown in Figure 5. Nanofibers created with electrospinning mimic the extracellular matrix (ECM) closely and have the same porosity, mechanical property, surface area-to-volume ratio (supports increased cell adhesion), pro-liferation, growth, and spreading [147]. The natural composition of bone is approximately 60 percent (dry weight) with the nanostructured composite having minerals such as calcium phosphate (CaP). The bone tissue regeneration process through the electrospinning method containing photo-bioactive (polyphenol) nanofiber formation is shown in Figure 5.

Plant-Based Nanoparticles (PBNPs) as a Promising Nanomedicine against COVID-19
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 (coronavirus disease 2019). The virus attachment to the host cell occurs with the viral spike (S) protein, and it also serves as the impassable pursuit for drug development against this deadly virus [162]. Plants contain natural products such as flavonoids, alkaloids, steroids, saponins, tannins, coenzymes, etc., that are present in abundance and are found in different parts of a plant such as the leaves, flowers, roots, stem, shoots, bark, and fruits as well in seeds. These phytochemicals are known as secondary metabolites, acting as a stabilizing and reducing agent for bio-reduction reactions to form novel therapeutics such as metallic nanoparticles (MNPs) [163]. PBNPs provide an alternative method for the antipathogenic property towards microorganisms (virus, fungi, bacteria, yeast) through reactive oxygen species (ROS) generation by the process of photocatalysis. The PBNPs can be used as a targeted drug delivery agent for the pulmonary system and can halt the interaction between the receptor (angiotensin-converting enzyme 2) and viral S protein. A recent study reported by Medicago and GSK showed a positive phase 3 trial of the PBNPs-derived vaccine against COVID-19. Medicago's reported plant-based NPs which was developed by using bizarre technology to make virus-like particles (VLPs) for its protein vaccines. These VLPs generally mimic the structure of the lethal, native structure of the virus, hence allowing the immune system to recognize it easily [164]. Additionally, another study showed that plant-derived silica NPs present on a mask minimizes the SARS-Cov-2 infectivity to zero [165].

Advantages and Disadvantages of Plant-Derived NPs
Plant-derived NPs are of significant use in the medicinal field, having biomedical applications. These NPs have a convenient shape and size and can be used for non-toxic and efficient drug delivery, anticancer treatment, wound healing, bone regeneration, and much more. NPs synthesis methods from plants are very novel and cost efficient, having no harm to nature or the environment. Due to the very tiny size, NPs can penetrate small capillaries, and loaded drugs can be efficiently absorbed into cells, allowing them to accumulate at their target sites. Moreover, the drug is retained at the active site for a longer period of time. It is possible to control the size of nanoparticles used in drug delivery and provide good protection for the drug. Apart from various advantages of plant-derived NPs, there are some disadvantages that need to be discussed. By inhaling air with nano particles in it for a few seconds, nanoparticles can cause inhalation problems, and other fatal diseases. As a result of their small sizes, NPs may also damage the lungs if inhaled for a prolonged period of time. Inhibition of autonomic equilibrium by nanoparticles directly impacting the heart and blood vessels [166]. Although plant-derived NPs are of significant interest, still, some methods that require chemicals are expensive and can also become toxic.

Discussion and Conclusions
Many researchers have a great deal of interest in the use of nanotechnology to create materials that are diverse in composition. Because nanotechnology generates materials with multi-dimensional structures typically controlled on the nanoscale range, applications of nanotechnology in medicine have sparked vast interest in cancer treatment wound healing, bone regeneration, and diagnosis. If more effective tumor-targeting strategies can be developed, nanoparticles will certainly play a more prominent role in cancer chemotherapy. In the biomedical field, nanoparticles with antimicrobial properties are widely used, and using secondary metabolites of plants for their synthesis and stabilization can substantially increase the effectiveness of metal and metal-oxide nanoparticles against microbes, in addition to making them biocompatible. For widespread medical use, the toxicity assessment of metal nanoparticles is imperative. Herbal extracts (due to the presence of abundant phytochemicals such as flavonoids, alkaloids, tannins, saponins, and other metabolites) serve as potential means for the production of nanomaterials via safer pathways. Various secondary metabolites embodying the extracts play the roles of stabilizing and/or reducing agents to restructure the nanoparticles (NPs) to have diverse applications in assorted fields, but predominantly in nanomedicine. Plant-derived NPs are even highly potent against the widely spread deadly disease COVID-19. In this way, the green initiatives of NPs synthesis are becoming more admired, and the topic anticipated to develop exponentially in the days ahead.