Recent Developments in the Facile Bio-Synthesis of Gold Nanoparticles (AuNPs) and Their Biomedical Applications

Figures & data

Figure 1 The types of green materials that can synthesize gold nanoparticles.

Figure 2 A simple illustration for the production of gold nanoparticles via green methods.

Table 1 The Advantages and Disadvantages of Different Green Materials for the Synthesis of Gold Nanoparticles

Green Materials	Advantages	Disadvantages	Applications	References
Plants	Synthesis method is simple and facile. It is easy to control the size and shape of the NPs by altering the reaction parameters and the reduction of NPs is relatively rapid and cost effective.	It is difficult to determine the reactive components in plants because plant extracts contain many organic compounds.	Biomedical applications, removal of dyes and heavy metals, catalysts.	^Citation22–Citation24
Fungi	It is possible to scale up the production of NPs using fungi because they are able to secrete large amounts of protein. Fungi are easier to culture as compared to other microorganisms.	Delicate preparation steps are needed to obtain mycelia free culture filtrates and it is difficult to genetically manipulate eukaryotic organisms to produce specific enzymes. Some species are pathogenic.	Antioxidants, catalyst for pollutant degradation.	^Citation94,Citation95,Citation100
Bacteria	Some species are resistant against heavy metals, thus, they can be exploited for biological metal recovery. Purer NPs are produced.	Not economical as bacteria culturing is tedious. The reduction process is also slow, ranging from hours to days.	Drug delivery agent, antibacterial agent.	^Citation21,Citation48,Citation103
Enzyme	Enzymes are commercially available in pure form. The purification of NPs is easier.	Some enzymes are expensive to purchase whereas the enzyme extraction process from microbes may be time consuming.	Anticancer agent, antimicrobial agent.	^Citation52,Citation104,Citation105
Biopolymers	Biopolymers consist of a variety of functional groups that can produce NPs and have a good combination of properties.	Different biopolymers have different reducing ability, therefore, it is necessary to test the reducing ability of the biopolymers.	Antifilarial therapeutics, catalyst, antioxidants, biosensors.	^Citation106,Citation111,Citation112,Citation114

Figure 3 Proposed mechanism for the reduction of gold nanoparticles where M⁺ is a gold (iii) ion while M⁰ is a zero valent gold.³³ “Reprinted from Journal of Advanced Research, 6, Anuradha, J, T Abbasi, and S. Abbasi, An eco-friendly method of synthesizing gold nanoparticles using an otherwise worthless weed pistia (Pistia stratiotes L.), 711-720, Copyright (2015), with permission from Elsevier.”

Figure 4 Some examples of plants: (A) Murraya koenigii Spreng, (B) Citrus, (C) Zingiber officinale, (D) Lonicera Japonica, (E) Garcinia mangostana and (F) abelmoschus esculentus used to synthesize gold nanoparticles.

Figure 5 Every part of a plant can be utilized as a green material for AuNP synthesis.

Table 2 Green Synthesized Gold Nanoparticles Using Different Parts of Plants

Part Used	Plant	Reactive Compound	Size (nm)	Shape	Reaction Time	Applications	References
Leaves	Artemisia vulgaris (Mugwort)	Polyphenols, flavonoids, terpenoids	50–100	Spherical, triangular, hexagonal	24h	Larvicidal activity against Aedes larvae	^Citation37
	Clitoria ternatea (Asian pigeonwings)	Alcoholic, amine groups, halocompou-nds	100	Rod	24h	Antibacterial, antioxidant	^Citation150
	Artocarpus hirsutus (Wild jack)	Polyphenols, flavonoids, terpenoids	5–40	Spherical	6h	Anticancer	^Citation136
	Justicia glauca (Thaasi murungai)	Lignans [(+)-pinoresinol, (+)-medioresinol], alkaloids, flavonoids, steroids (sitosterol-3-0-glucoside), terpenoids	32	Hexagonal, spherical	1h	Electrode for selective voltammetry	^Citation17
	Murraya koenigii Spreng (Curry leaves)	Polyphenols, quercetin, quercetin-3-glucoside, flavonoids	20–40	Spherical	152mins	Fluorescent marker	^Citation8
	Terminalia arjuna (Arjun tree)	Arjunetin, leucoanthoc-yanidins, hydrolyzable tannins	20–50	Spherical	15mins	Plant tissue culture	^Citation61
	Memecylon umbellatum (Iron wood)	Protein, saponins, polyphenols, carbohydrate	15–25	Spherical, triangular, hexagonal	18h	–	^Citation62
	Coreopsis lanceolate	Antioxidants like sugars, flavonoids	20–30	Spherical, quasi spherical	15mins	Detections of aflatoxins	^Citation140
	Olive	Proteins, oleoropein, apigenin-7-glucoside, luteolin-7-glucoside	50–100	Triangular, spherical, hexagonal	20mins	-	^Citation63
	Cassia auriculata (Matura tea tree)	Polysaccharides, flavonoids	15–25	Spherical, triangular,hexagonal	10mins	–	^Citation64
	Mangifera indica (Mango)	Terpenoids, flavonoids, thiamine	17–20	Spherical	2mins	–	^Citation65
Fruits	Lantana camara (Wild sage)	Ursolic acid, iridoid glycosides, mono- and sesquiterpe-nes, flavonoids	150–300	Triangle	72h	–	^Citation28
	Citrus maxima (Pomelo)	Polypeptides/proteins, terpene, ascorbic acid	15–35	Spherical	5mins	Catalyst	^Citation66
	Sterculia acuminate (Pola plant)	Phenolic compounds	9.37–38.12	Spherical	4mins	Catalyst	^Citation58
	Citrus (Lemon, tangerine, orange)	Citric acid, proteins	32.3, 43.4, 56.7	Spherical, triangular	10mins	-	^Citation67
	Pear	Sugars, amino acids, proteins	20–400	Triangular, hexagonal, polyhedral	20mins	–	^Citation68
Rhizome	Yam bean	–	200–400	Triangular	24h	Photodynamic and photo thermal therapy	^Citation69
	Acorus calamus (Sweet flag)	Asarone, caryophylle-ne, isoasarone, methyl isoeugenol, safrole	10	Spherical	–	UV-blocking agent	^Citation70
	Turmeric	Phenolic (curcumin), triterpenoids, alkaloid, sterols	5–60	Oblong spherical	–	–	^Citation35
	Zingiber officinale (Ginger)	Oxalic acid, ascorbic acid, phenylpropa-noids, zingerone	10–20	Spherical, triangular, truncated triangular, hexagonal	20mins	Antibacterial	^Citation71
	Panax ginseng C.A. Meyer (Korean red ginseng)	Saponin glycoside (ginsenoside), polysaccha-rides, flavones, peptide glycans	2–40	Spherical	2.5h	Anticancer	^Citation72
Flower	Lonicera Japonica (Japanese honeysuckle)	Amino acids	8	Triangular, tetrahedral	1h	–	^Citation73
	Nyctanthes arbortristis (Night flowering jasmine)	alkaloids, flavonoids	15–25	spherical	30mins	–	^Citation74
Peels	Musa paradisiaca (Banana)	Phenolic compounds, gallocatechin, dopamine	50	Spherical	20mins	Antibacterial, anticancer	^Citation42
	Mangifera indica Linn (Mango)	Phenols, carboxylic acids	3.26–21.68	Quasi-spherical	25mins	Non-cytotoxic to normal cells	^Citation75
	Terminalia arjuna (Arjun tree)	Polyphenols	60	Triangular, hexagonal, pentagonal	20mins	-	^Citation76
Seed	Cocoa	Polyphenols	150–200	spherical	-	photothermal therapy	^Citation77
	Abelmoschus esculentus (Okra)	Proteins, polysaccha-rides, glycoprotein	45–75	Spherical, uneven shape	10mins	Antifungal	^Citation78
Bark	Guazuma ulmifolia (Bay cedar)	Tannins, proanthocya-nidins, precocene, catechins	20–25	Spherical	10mins	Catalyst, DNA binding, antibacterial, antifungal, anticancer	^Citation156
	Willow tree	Tannins, alkanoids, flavonoids, alkaloids	15	Spherical	30mins	Colorimetric sensor	^Citation142
	Acacia nilotica (Gum Arabic tree)	Protein, phenols, tannins, terpenoids, saponins	10–50	Unshaped, quasi-spherical	10mins	Electrochemical sensor	^Citation43
Others pulp	Capsicum annuum var. grossum (Green pepper)	Proteins, carbohydrates	6–37	Triangular, hexagonal, quasi-spherical	10mins	Catalyst	^Citation32
Biomass	Momordica cochinchinensis (Lour.) Spreng (Gac)	Proteins	10–80	Spherical, oval, triangular	12h	Photo catalyst	^Citation79
Galls	Pistacia integerrima (Zebra wood)	Monoterpenes, triterpenoids, sterols, dihydromal-valic acid	20–200	Grain like	–	Enzyme inhibition, muscle relax, sedative activities	^Citation157
Nut	Areca catechu (Pinang palm)	Polyphenols, fats, proteins, carbohydrate, flavonoids	Spherical	13.70	5h	Catalyst, antioxidant, antibacterial, anticancer	^Citation80
Latex	Hevea brasiliensis (Para rubber tree)	isoprene, proteins	50	Spherical, triangular	30mins	–	^Citation81
Palm oil mill effluent	Palm oil	Proteins, flavonoids, reducing sugars, alkaloids	13–25	Spherical	1h	Removal of mercury	^Citation36
Whole plant	Macrotyloma uniflorum (Horse gram)	Proteins, carbohydrate, antioxidant	14–17	Spherical	–	–	^Citation82

Figure 6 TEM micrographs of gold nanoparticles prepared with (A) 100, (B) 200 and (C) 400 lL of a P. dactylifera extract. The corresponding histograms are represented by (A’), (B’) and (C’).⁸³ “Reprinted from Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 121, Mervat F. Zayed,Wael H. Eisa, Phoenix dactylifera L. leaf extract phytosynthesized gold nanoparticles; controlled synthesis and catalytic activity, 238-244, Copyright (2014), with permission from Elsevier.”.

Figure 7 Gold nanoparticles can be synthesized via different approaches when using bacteria.

Table 3 Cancer Cells That Have Been Targeted Successfully by Gold Nanoparticles

Cancer Type	Cell Line	References
Skin	B16-F10	^Citation45
Breast	MCF-7, T47D	^Citation45,Citation130–Citation132
Lung	A549	^Citation42,Citation45,Citation87,Citation131
Gastric	NCL-N87	^Citation100
Liver	Hep3B	^Citation133
Colon	HCT-116	^Citation38
Cervical	HeLa, Hep2	^Citation90,Citation129,Citation134
Bone	MG-63	^Citation133
Tumor	Ehrlich ascites carcinoma, HNGC-2, MKN-28	^Citation130,Citation133

Figure 8 Schematic diagram showing the killing of cancer cells by gold nanoparticles.

Figure 9 (A) Fluorescence confocal images of HepG2 cells after incubation with AuNCs@ew–Hg(II) for 0, 12, 15, 21, 30 and 45 min. (B) Fluorescence confocal images of normal cells (HT22 cells) after incubation with AuNCs@ew–Hg(II) for 1.0 h. The images in the left column show the fluorescence of the AuNCs@ew added to HT22 cells; the middle column shows the DIC images of cells in bright field; and the right column shows the merging of the two previous images.¹³⁹ “Reprinted from Sensors and Actuators B: Chemical, 240, Lu Tian, Wenjing Zhao, Lin Li, Yaoli Tong, Guanlin Peng, Yingqi Li, Multi-talented applications for cell imaging, tumor cells recognition, patterning, staining and temperature sensing by using egg white-encapsulated gold nanoclusters, 114-124, Copyright (2017), with permission from Elsevier.”

Table 4 The Shape of Gold Nanoparticles and their Applications

Shape of AuNPs	Applications	References
Spherical	Photothermal therapy, drug delivery and cancer therapy	^Citation159–Citation161
Plate particles	Electrochemical sensor	^Citation162
Hollow particles	CT imaging cancer therapy	^Citation163
Triangular	Photodynamic and photothermal therapy, immunosensor and catalyst	^Citation32,Citation69,Citation164
Hexagonal	Catalyst	^Citation32
Nanorod	Marker and biosensor	^Citation138
Nanoflowers	Biosensor for diseases and removal of dye or heavy metal	^Citation165
Network dendrite	Antifungal and antibacterial agent	^Citation158

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