Anticancer activities of silver nanoparticles (AgNPs) synthesized from plants.
Abstract
Silver nanoparticles (AgNPs) synthesis from plants that already have been reported for medicinal purposes demonstrated better efficacy for curing diseases. Recently, a number of researches have been reported where AgNPs act as promising antibacterial and anticancer agent. Biosynthesized silver nanoparticles (AgNPs) are a type of environmentally friendly, cost-effective, and biocompatible substance that has gotten a lot of attention in treatment of cancer and inhibition of pathogenic microbes. In this chapter, a comprehensive report on the recent development of AgNPs as nanomedicine synthesized from plant extracts. The role and mechanism of AgNPs as antibacterial and anticancer agent was reported that leads towards development of targeted nannomedicines to treat infectious diseases and world most challenging disease like cancer. Reported literature give imminence importance of AgNPs and demonstrated more potency to treat cancer and bacterial infections.
Keywords
- silver nanoparticles
- biolabeling
- conjugation
- phagocytosis
- polydispersity
1. Introduction
Silver has been used widely from ancient times as it is a noble metal. Hippocrates advocated for the use of silver in the treatment of sickness and for healing purposes [1]. Silver is found abundantly in nature with multiple biological and biochemical properties making silver most suitable candidate for the biomedical applications, can be used as an antiseptic, part of medicines, antimicrobial efficacy, pharmaceutical industry, Food preservation, cosmetics, biolabelling, and optical properties. AgCl and AgNO3, ionic forms of silver, caused cardiac alterations in rats, such as left ventricular hypertrophy, hypersensitivity, and inhibition of normal fibroblast function [2]. Silver nanoparticles (AgNPs) are comparatively safe and more effective in medical treatment to silver ions [3].
Recently, nanotechnology has played a critical role in biomedical, diagnosis, treatments, the industrial sector, scientific purpose, and environmental protection [4]. Nanomaterials have a size range of 1–100 nm, or particles with at least one dimension smaller than 100 nm [4]. Due to unique physicochemical and biological characteristics, such as large surface area to volume ratio, excellent surface plasmon resonance, conjugation with various ligands to obtain desired property, inhibition against microbes, potent toxicity towards cancer cells, catalytic operations, silver nanoparticles are one of the most widely studied metal nanoparticles for a variety of scientific purposes. Due to very small size they penetrate the blood capillaries and tissues and become more effective in cancer treatment. Moreover they carry the multiple drugs on their large surface area and have capability to modify and combine chemically. Antimicrobial and anticancer activities of green synthesized AgNPs is due to phytoconstituents attached on their surface [5]. Several research studies have been conducted a green method to synthesize a range of metallic nanoparticles in concern with growing worldwide burden of cancer that showed potential anticancer effect against a range of cancer cell types [6]. Unicellular or multicellular living organisms are typically with 10 μm, so AgNPs in small size (1–100 nm) can interact with cell wall of bacterial, viral, and fungal pathogens and their active nano-complexes can penetrate and break the external capsule. The permeability of the plasma membrane to small-sized AgNPs permits them to accumulate in cell compartments. Phagocytosis, endocytosis, or micropinocytosis is the uptake mechanisms of nanoparticles in eukaryotic cells [7].
The rising applications of AgNPs in field of oncology and microbiology, present chapter emphasizes the significant antibacterial and anticancer properties of AgNPs synthesized by the green approach, recent developments and finding new perspectives in nanomedicine. In comparison with other methods, Ram Prasad’s methods have been shown to be better due to their slow kinetics and ability to manipulate crystal growth and stabilization in a better way. The biogenetic synthesis uses plant extracts in aqueous form to create noble nanoparticles, as the extracts contain more reducing agents than plants. The availability of silver nanoparticles and their various metabolites makes plant-mediated silver nanoparticle synthesis a preferable method [8]. There are several phyto-constituents that are believed to reduce silver ions, including tannins, terpenoids, flavonoids, ketones, aldehydes, amides, and carboxylic acids. Plant extracts (chemical composition, amount, conjugation method) and nanoparticles (type, size, shape, polydispersity, etc.) play an influential role in the properties of a bioconjugate method [9].
In addition to being expensive to manufacture, the silver ion method has not been demonstrated to be clinically effective in randomized controlled trials and cannot be used with oxidizing solutions such as hypochlorite or H2O2 [10]. There are several drawbacks to the generation of silver nanoparticles (AgNPs) using a tube furnace, including the fact that it occupies a large space, consumes a lot of energy, raises the temperature in the surrounding environment, and requires a lot of time to achieve thermal stability. To achieve a stable operating temperature, a tube furnace typically requires several kilowatts and several time of preheating [11]. The polysaccride method is very temperature sensitive because the binding between the silver nano particles is very weak. If the temperature is increased slightly then the reversible reaction is started and the separation of the silver nano particles is started so the nano particles are unstable [12].
2. Applications and importance of silver nanoparticles
Nanoparticles and nano-composites synthesized from plants containing noble metals, silver nanoparticles are widely used metal due to incredible potential and significant usage. The diverse chemical and physical nature of AgNPs suggests potential uses in the environment and for the well being of human life, promoting one health program for example cover the field of agriculture, food industry, medicine, and for the better human health (Figure 1) [13, 14, 15]. In the treatment of cancer cells, AgNPs are used as therapeutic agents due to cellular oxidative and apoptotic potential [15, 16]. AgNPs offer new uses due to their size-dependent actions and capacity to form various complexes with natural or synthetic molecules [17, 18, 19].
AgNPs are the most studied zero-dimensional nanoparticles for their remarkable and unparalleled uses in pharmaceutical science, infectious problems, wound care, antimicrobial, food packaging, and the cosmetic sector [20]. In recent years, biosynthesized AgNPs have shown potent larvicidal, bactericidal, fungicidal, antioxidant, antiviral, antidiabetic, and anticancer activities [21]. There are approximately 383 commercialized nano silver-based products on the market worldwide, accounting for 24% of all nano products [22].
2.1 Silver nanoparticles as anticancer agent
Cancer is one of the most challenging diseases to treat, and defined as the uncontrollable division of altered cells. It is the leading cause of mortality and about 70% deaths in middle and low income countries and 68% population suffer due to cancer [23]. Globally cancer burden will be rise up to 27 million by 2040 [24]. Cancers most commonly diagnosed in the human population include lung, thyroid, cervical, liver, stomach, brain tumors, prostate, uterine, and breast cancers [19]. The most predominantly prevalent cancer are breast and prostate cancer that effect women and men, respectively. The field of cancer nanobiotechnology has provided new direction to detect, diagnose, and treat cancer [25]. AgNPs produced through green method with phytochemical covering give them more efficacy than AgNPs produced through chemical method. The ability to combine AgNPs inherent anticancer property with the pharmacological anticancer effects could be the key to treating malignancies that have stopped responding to chemotherapy or radiotherapy. Metal-based AgNPs have been found to be pro-oxidative in a variety of cancer cell types. The phytoconstituents berberine isolated from plants in combination with AgNPs showed synergistic anticancer activity [26]. Several studies in the published literature have looked into the methods by which AgNPs exhibit anticancer action. Among studied cancer cell lines most of the silver nanoparticles are studied against breast cancer cell line MCF-7. The size of AgNPs evaluated for anticancer ranged from 5 to 100 nm; with varying shapes such as spherical, cubical and hexagonal. The IC50 values of green synthesized AgNPs extracts against studied cell lines ranged from 6 to 1200 μg/mL. Some important studies regarding
Plant used | Part used | Size (nm) and shape of AgNPs | Cancer cell line | IC50 value (μg ml − 1) | Reference |
---|---|---|---|---|---|
Leaves | 10 (spherical) | A549 lung cancer cells | 15 | [27] | |
Leaves | 59 (spherical) | MCF-7 | 40 | [28] | |
Whole plant | 10–60 (spherical) | MCF-7 | 12.3 | ||
Fruit | 5–8 (spherical) | MDA-MB-231 | 6 | [29] | |
leaves | 8 (spherical) | MDA-MB-231, HCT-116 and PANC-1 | 0.54–0.00025 | [30] | |
Rhizome | 9.2 (spherical) | MCF-7, Bladder (5637) | 9.3–1,13.0 | [31] | |
callus | 4.2 (spherical) | MDA-MB-231 | 50 | [32] | |
Leaves | 60 (spherical) | MCF-7 | 9.63 | [19] | |
Whole | 9.39–25.89 (spherical) | MCF-7 | 27.79 | [33] | |
Seed coat | 41.90 (spherical) | MCF-7 | 30 | [34] | |
Peel | 59 (spherical and polygonal) | Colo-259 | 17.4 | [35] | |
seed | 20–51 (spherical) | HT-29 | 150.8 | [36] | |
peel | 52 (spherical) | HT-29 | 7 | [37] | |
Aerial parts | 328.6–284.5 (spherical) | HCT116 | 99.35 | [38] | |
Leaves | 100 (spherical) | HCT116 | 1.7 | [39] | |
Leaves | 10–68 (spherical) | A549 | 65.17 | [40] | |
leaves | 6–45 (spherical) | A549 | 5 | [41] | |
leaves | 16.92 (spherical) | A549 | 86.23 | [42] | |
Peel | 8–22 (spherical) | H1299 | 5.33 | [43] | |
Aerial parts | 33 (cubical) | HeLa | 23 | [44] | |
Leaf | 81 (cubical) | HeLa, PANC-1 | 31.5–1.84 | [45] | |
leaf | 40 (spherical) | HeLa, SiHa | Dose dependent | [46] | |
leaf | >100 (spherical) | HEK-293, HeLa | 0.062–1.98 | [47] | |
leaf | 46.1 (spherical) | HeLa | 100 | [41] | |
leaf | 100–800 (spherical) | HePG2 | 31.25 | [48] | |
leaf | 15.9 (spherical) | PA-1 | 25 | [46] | |
Whole plant | 30–50 (spherical) | PC3 | 6.8 | [49] | |
Peel | 9–32 (cubical) | PC3 | 10 | [43] | |
Leaf | 25.71 (spherical and cubical) | COLO205, LNCaP | 39.28–24.33 | [50] | |
leaf | 100 (spherical and hexagonal) | LNCaP | 50 | [51] | |
Leaf | 18.93 (spherical) | AsPC-1PANC-1 | 312–1295 | [36] | |
leaf | 35–69 (spherical) | HePG2 | 70 | [41] | |
leaf | 59 (spherical) | MCF-7, A-549 and SCC-40 | 10 | [35] | |
Fruit shell | 20–30 (spherical) | MCF-7 | 120 | [24] | |
Smaller size (spherical) | HCT-116 | 48.84 | [52] | ||
Stem | Small size u-shaped | Vero cells | 31.25 | [53] | |
Leaf | 125 | ||||
Leaf | 250 | ||||
Fruits | 21 to 173 nm | MDA MB-231 | 16.8 μg/ml. | [54] | |
Leaf | 11.1–45.4 | A459 | 42.70 | [55] | |
Leaf | 35–50 | AGS and MCF-7 | 240 | [56] | |
Leaf | 20 spherical | HepG2 | 50 | [57] | |
leaf | 20–50 | A549 and PA1 | 28 and 30 μg/mL | [58] | |
Bee pollens | Leaf | 44 | MCF-7 | 90 | [59] |
chitosan, | Leaf | 23 | MDA-MB–231 | 4.6 | [60] |
Fruit | 43 spherical shape | HT-29 and MCF7 | 155 and 179 | [61] | |
Stem | 7 nm–14 spherical | A549 | 46.54 | [62] | |
Leaves | 8 spherical | MCF-7 | 90 | [63] | |
MDA-MB-231 | 65 | ||||
U87 | 80 | ||||
DBTRG, | 90 | ||||
Leaves | 32 spherical shape | MCF-7 | 25 | [58] | |
Leaves | 100 | HeLa | 7.71 | [64] | |
Hep G2 | 12.44 | ||||
Aerial part | 10–30 nm/spherical | MCF-7 | 3.04 | [65] | |
Leaf | 48 nm/− | MCF-7 | 42.5 | [55] | |
Leaf | 68.06 nm/cubic, pentagonal, hexagona | MCF-7 | 31.5 | [65] | |
Flower | 12 nm/spherical, pentagonal | MCF-7 | 20 μg/mL | [66] | |
Leaf | 40 nm/spherical | MCF-7 | 10 | [59] | |
Leaf | 37 nm/spherical, rod, triangular, hexagonal | MCF-7 | 30.5 | [67] | |
Leaf | 7.39 nm/spherical | MCF-7 | 2.4 μg/mL | [68] | |
Leaf | 5–45 nm/spherical | MCF-7 | 7 | [57] | |
Root | 20–118 nm/spherical | MCF-7 | 23.89 | [60] | |
Leaf | 7.3 nm/irregular | MCF-7 | 31.2 | [69] | |
30–60 nm/spherical | MCF-7 | 30 | [70] | ||
Root | 46 nm/spherical | MCF-7 | 67 | [71] | |
Fruit hull | 46 spherical | MCF-7 | 50 | [34] | |
Root | 27.5 nm/spherical | MCF-7 | 28 | [47] | |
Leaf | 22 nm/spherical | MCF-7 | 20 | [72] | |
fruit | 41.90 nm/spherical, polygonal | MCF-7 | 30 | [46] | |
Fruit | 40 nm/spherical | MCF-7 | 10 | [73] | |
Fruit | 5–20 nm/spherical | MCF-7 | 70 | [74] | |
Leaf | Mean 22.85 nm/spherica | MCF-7 | 20 | [75] | |
Needles | Mean 75.1 nm/spherical | MCF-7 | 0.25 | [76] | |
Whole | 56 nm/spherica | MCF-7 | 37 | [71] | |
LEAF | 20–80 nm/spherical | HNGC2 | 67 | ||
Leaf | 2–18 nm/triangular, hexagonal | shia | 4.1 | [77] | |
Leaf | 78 nm/cubical, spherical | HeLa | 300 | [78] | |
Leaf | 16.57 nm/Spherical | HCT-116 | 30 | [79] | |
Leaf | Spherical | HT29 | 85 | [80] |
Although AgNPs of large size >100 nm can be more effective but small size <10 nm penetrate the cell, get localized inside the nucleus easily and can induce cytotoxicity at greater level as reported by Avalos et al. that smaller size nanoparticles exhibit more cytotoxicity than larger size in MTT assay and lactate dehydrogenase assays [82]. The mechanism involved behind inducing cytotoxicity is (i) interruption in cellular respiration and DNA replication due to uptake of free silver ions (ii) production of free silver radicals and reactive oxygen species (ROS) (iii) damage to cell membrane [83]. AgNPs induce ROS production and reduce glutathione (SGH), nuclear factor kB (NF-kB) and tumor necrosis factor-alpha (TNF-1) levels within cells). Increasing levels of superoxide radicals disrupt the mitochondrial signal transduction pathway, resulting in apoptosis [84]. The increase level of reactive oxygen species and decrease glutathione elicit damage to different components of cell such as breaking of DNA, peroxidation of lipid membrane and protein carbonylation. Apoptosis occurs when caspases 3 and 9 are activated as a result of changing mitochondrial membrane potential. After that, it activates c-Jun NH2terminal kinase (JNK), which causes DNA breaks to cause cell cycle arrest and the creation of apoptotic bodies [85]. AgNPs prepared from plants increase the sub-G1 phases of cell cycle and exhibit potent cytotoxicity. Chang et al. demonstrated link between sub-G1 arrests in cancer cells treated with curcumin showed more apoptosis suggested that AgNPs induced apoptosis in cancerous cells by prolonged sub-G1 phase [86]. This implies that the enhanced sub-G1 arrest of cancerous cells, which is connected to the induction of apoptosis, may be resulting in the death of cancer cells due to AgNPs application. In addition, green synthesized AgNPs prevented the formation of new cells induced by vascular endothelial growth factor (VEGF). After penetrating into the cell, AgNPs inhibited VEGF and through Src-dependent pathway the vascular permeability 1 L-1βinduced occured. [87]. Due to this anti-angiogenic efficacy AgNPs recommended as a new gateway of treatment for cancer. Another mechanism suggested for the anticancer potential of AgNPs is autophagy-induced cell breakdown, which results in cell death. Additionally, because autophagolysosomes accumulate in cancer cells and are more prevalent there, greenly produced AgNPs encourage autophagy, which ultimately results in cell death [30].
2.2 Silver nanoparticles as antibacterial agent
Silver nanoparticles have antibacterial properties and they auspiciously appear to be more potent and efficient antimicrobial agents than other nanomaterials from noble metals, due to their unique properties such as a large surface to volume ratio, toxicity, interaction with phosphorus and sulfur compounds in the cell [88]. These characteristics make them excellent agents for treating a variety of microbial infectious complaints, as well as for overcoming microbial resistance to conventional medicines, whether used in single or in combination with other therapeutic formulations [89]. The synergistic action of nano-silver and a broad variety of phytoconstituents exhibit wide range of antibacterial qualities, as silver nanoparticles are easily manufactured from plant extracts with extraordinary stability and eco-friendly approach. According to a report antimicrobial agent containing silver ions can damage the external membrane of targeted cell by reacting with proteins (thiol group) resulted in inactivation of bacterial enzymes. Silver reduces DNA replication and uncouples electron transport from oxidative phosphorylation when applied. As a result it interferes with membrane permeability and inhibits the respiratory chain enzymes and kills the microbes at very low concentration [90, 91]. AgNPs have suppressed the growth of bacteria at the minimum inhibitory concentration (MIC) for example;
Plant used | Concentration (μg/ml) | Bacteria | ZI (mm) | Reference |
---|---|---|---|---|
12.50 | 12 | [95] | ||
0.25 | 36 | [94] | ||
1 | 28 | |||
2 | 15 | |||
4 | 23 | |||
8 | 26 | |||
16 | 41 | |||
10 | 77.57 | [96] | ||
89.21 | ||||
93.64 | ||||
10 | 73.83 | |||
83.31 | ||||
93.12 | ||||
15.50 | 92.62 | |||
80.76 | ||||
96.03 | ||||
10 | 8 | [97] | ||
12.5 | 2 | [98] | ||
100 | 6 | |||
5 | 11 | [99] | ||
10 | ||||
10 | [100] | |||
7 | [101] | |||
8 | ||||
6 | ||||
6 | ||||
8 | ||||
5 | ||||
5 | ||||
5 | ||||
4 | ||||
6 | ||||
6 | ||||
4 | ||||
100 | 6.5 | [102] | ||
0.05 | 2.3 | [103] | ||
0.1 | 3.1 | |||
0.05 | 2.1 | |||
0.1 | 2.7 | |||
15 | 10 | [37] | ||
30 | 17 | |||
60 | 29 | |||
15 | 9 | |||
30 | 11 | |||
60 | 14 | |||
50 | 9 | [104] | ||
11 | ||||
11 | ||||
18 | ||||
30 | ||||
16 | ||||
20 | [105] | |||
100 | 12.44 | [106] | ||
28.64 | ||||
50 | 12.5 | [107] | ||
21 | 11 | [108] | ||
14 | ||||
14 | ||||
14 | ||||
12 | ||||
14 | ||||
100 | 2 | [109] | ||
150 | 3 | |||
25 | 15 | [110] | ||
50 | 17.50 | |||
75 | 17 | |||
7 | 2.7 | [111] | ||
2.5 | 4 | [54] | ||
5 | 7.5 | |||
10 | 11 | |||
20 | 14 | |||
50 | 22 | |||
2.5 | 3.8 | |||
5 | 7 | |||
10 | 10 | |||
20 | 11 | |||
50 | 19 | |||
20 | 11 | [55] | ||
15 | ||||
20.66 | ||||
15.33 | ||||
20 | ||||
10 | 11 | [101] | ||
20 | 13 | |||
30 | 14 | |||
40 | 17 | |||
10 | 10 | |||
20 | 12 | |||
30 | 13 | |||
40 | 14 | |||
10 | 10 | |||
20 | 13 | |||
30 | 15 | |||
40 | 16 | |||
100 μg/mL | 18 | [59] | ||
18 | ||||
17 | ||||
11 | ||||
60 | 17 | [60] | ||
18 | ||||
12 | ||||
11 | ||||
15 | ||||
40 | 29 | [62] | ||
24 | ||||
23 | ||||
5 | 7.2 | [63] | ||
7.9 | ||||
7.4 | ||||
25 | 24 | [102] | ||
17 | ||||
50 | 10 | [103] | ||
8 | ||||
25 | 10 | [77] | ||
12 | ||||
08 | ||||
50 | 12 | [103] |
2.3 Antifungal activity of silver Nano particles
Drug resistance by pathogenic fungi has been continuously increasing, so it is necessary to develop new antifungal agent. The antifungal agent was present in the form of the chemically, physically and, biologically. The green plants which caring affective metabolites and particles which use against the fungus disease. There are the many nano particles which use against the fungi but Silver nano particles have the drastic affect against the many disease which is caused by the fungi [25]. In many study reported that the AgNPs as antifungal agent in treating fungal infectious diseases [112]. This disease badly affected the human and the plants as well. Silver nanoparticle are very effective against the four pathogens
Plant name | Concentration μg | Fungus | Reference | |
---|---|---|---|---|
75 | 13 | [115] | ||
15 | ||||
90 | 22 | [77] | ||
50 | 14.3 | |||
50 | 9.80 | |||
red curran | 30 | 12 | [116] | |
26 | ||||
50 | ||||
923.4 | 1.9 | [117] | ||
3.5 | ||||
50 ppm | 47 | [118] | ||
100 ppm | 52 | |||
0.32 mg/mL | 08 | [119] | ||
10 mg/mL | 11 | |||
0.32 mg/mL | 07 | |||
10 mg/mL | 10 | |||
1.8 mg/mL | 26.6 | [120] | ||
11 | 15.5 | [121] | ||
14.5 | ||||
9.5 | ||||
12 | ||||
5 μL | 7.7 | [122] | ||
10 μL | 11 | |||
5 μL | 7 | |||
10 μL | 10 | |||
5 μL | 10 | |||
10 μL | 18 | |||
100 | 7 | [123] | ||
0.01 mmol\ml | 14 | [124] | ||
18 | ||||
22 | ||||
21 | ||||
15 | ||||
0.02 mmol\ml | 16 | |||
21 | ||||
27 | ||||
25 | ||||
17 | ||||
15 μg /mL | 81.1 | [125] | ||
83 | ||||
88.6 | ||||
80 | ||||
25 μg /mL | 20.1 | [126] | ||
20.6 | ||||
15.1 | ||||
16.4 | ||||
18.4 | ||||
20 μg /mL | 87 | [127] | ||
50 μg /mL | 46 | [128] | ||
100 μg /mL | 54 | |||
150 μg /mL | 54 | |||
plant essential oil | 20 μg /mL | 11.33 | [129] | |
20 μg /mL | 13.27 | |||
9.87 | ||||
14.66 | ||||
15.17 | ||||
maize | 25 | 0.021 | [130] | |
Maize | 47 g | 62.5 | [131] | |
250 μg/mL | 34 | [132] | ||
6.25 | 10 | [133] | ||
12.5 | 13 | |||
25 | 16 | |||
50 | 19 | |||
Grass waste | 2 | 20 | [134] | |
5 | 38 | |||
10 | 60 |
3. Conclusions
Due to the vast range of activities and unique physical and chemical characteristics, silver nanoparticles are currently the subject of in-depth research. AgNPs are effective anticancer agents because they affect the cell cycle, prevent the growth of cancer cells, cause oxidative stress, and promote apoptosis [135, 136]. They protect against bacterial infections and showed potent antibacterial effect at minute concentrations. Due to the weakened immunological resistance of cancer patients, such antimicrobial protection is preferred during chemo- and radiotherapy. Most of the literature for use of AgNPs as antibacterial and anticancer agent is quite reported recently in present century showing that nanomedicine has made many advances in ongoing years and still there need to explored this field [137, 138, 139]. In order to gain unique insights and improve silver NP characteristics, additional research on AgNPs needs to be done.
Future applications may involve certain contentious concerns, like dose for various tissues; side effects from therapy, tissue-specific biocompatibility, or microbial resistance to NPs. AgNPs have some actions that seem to be dual or even contradictory depending on the situation. Examples include anti- or pro-oxidative, biosensing or bioresisting activity depending on the type of cell or living organism. Before being added to cells, NPs must be thoroughly described and their physical and chemical characteristics must be understood. These characteristics are mostly the product of various AgNP synthesis techniques, and only nontoxic ones should be favored in bioassays involving living models.
Author contributions
Muhammad Adnan and Ruqia Nazir, Sakina Mussarat conceived the idea of chapter, helped in writing and provide useful suggestions. Sakina Mussarat and Attique ur Rehman Khan participated in writing of the manuscript, and performed all literature surveys, designed the figures and reviewed the literature. All authors were involved in revising the chapter content, read, and approved the final draft.
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