The current trends in the green syntheses of titanium oxide nanoparticles and their applications

ABSTRACT

Nanotechnology is a new star in the science horizon with many valuable applications and promises to offer. It includes the synthesis and utilization of nanostructure materials ranging from 1 to 100 nm. Mostly these materials are generally (or “could be”) produced via the laborious and hazard-prone physical and chemical methods but the green synthesis approaches easier, safe and scalable have been recently developed. Among other metal oxides nanoparticles, Titanium oxide (TiO₂) nanoparticles have been mostly exploited for their photocatalytic, antimicrobial and antiparasitic applications. A diverse set of biological entities are used to reduce the precursor metal salt into respective nanoparticles. The secondary metabolites present in organisms such as plants or microbes are involved in the bio-reduction and capping processes. This article will provide an overview of the green synthesis of TiO₂ NPs from different biological extracts such as plants, microbes and biological products as well as their potential applications.

GRAPHICAL ABSTRACT

KEYWORDS:

• Titanium
• nanoparticles
• nanotechnology
• antimicrobial
• photo catalysis

1. Introduction

Nanotechnology is an emerging field that has got phenomenal interest in the last few decades. The word “nano” means small, 1 billionth part of a meter Hussain et al. ( 1). The smaller size and unique surface chemistry of these nanostructures have been already exploited in medicine, nutrition, and energy Chandran et al. ( 2). Amongst other nanoparticles Titanium Oxide nanoparticles also exhibit unique surface chemistry and morphologies. It is used in synthesis of tints, textiles, papers, plastics, cosmetics, and foodstuffs Muhd Julkapli et al. ( 3). Colloidal TiO₂ NPs are used in degradation of toxic chemicals in water Centi et al. ( 4), Pirkanniemi and Sillanpää ( 5). Mostly TiO₂ NPs are produced via physicochemical methods like chemical vapor deposition, micro emulsion, chemical precipitation, hydrothermal crystallization, and sol–gel methods Muhd Julkapli and colleagues ( 3), Valencia et al. ( 6). All these methods require high temperature, pressure and toxic chemicals which limits their production and potential medical uses Chen et al. ( 7). Hence, an eco-friendly and cost-effective approach is needed to synthesize these nanosized materials on larger scale with lesser hazards Jayaseelan et al. ( 8). This could be possibly accomplished by using biological extracts as a reducing agent; the green synthesis approach. The same reducing agent can synthesize more than one type of metallic nanoparticle Edmundson et al. ( 9). Moreover, nanoparticles with better morphology and stability are also produced Suresh et al. ( 10), Bhainsa and D'souza ( 11), Song and Kim ( 12). Mostly water-soluble metabolites are involved in the reduction process. The bio-mediated TiO₂ NPs have many applications such as diseases diagnostics, treatment, and manufacturing of surgical tools, tissue engineering, imaging, sensing, energy production and agriculture Jayaseelan and colleagues ( 8), Dobrucka ( 13), Órdenes-Aenishanslins et al. ( 14). This mini-review describes a brief overview of the research on bio-mediated TiO₂ NPs from different plants, bacteria, fungi and other biological derivatives. Moreover, the potential applications of bio-mediated TiO₂ NPs are also here emphasized.

2. Green synthesis of TiO₂ nanoparticles from different sources

In attempt to develop a cost effective, eco-friendly and energy efficient approach, researchers have exploited the potential of biological resources for the synthesis of TiO₂ NP Pantidos and Horsfall ( 15). The complete biosynthesis process as shown in Figure 1, a simple precursor salt is mixed with biological extract; the metabolites present in the extract can then reduce and stabilize the bulk metal into elemental form following various mechanical steps. This biosynthetic approach offers many advantages and has emerged as a simple, safe and feasible substitute to chemical and physical methods Nadeem et al. ( 16), Asha et al. ( 17), Marimuthu et al. ( 18), Jalill et al. ( 19), Singh ( 20). Apart from these, biological approach can effectively catalyze the synthesis process at any scale and condition. Moreover, NPs with controlled size and shape can also be produced Bao et al. ( 21). Owing to these benefits, numerous researchers have intended to explore diverse species for their potential to synthesize TiO₂ NPs.

Figure 1. Reduction mechanism of TiO₂ NPs.

2.1. Plants

Among the studied biological species, plants are considered as one of the most suitable candidates for the synthesis of NPs as they are cost effective, safe and easily available Mittal et al. ( 22). A diverse array of compounds in plants (phenolic acids, alkaloids, proteins and among them enzymes, as well as carbohydrates) regulate through reduction and stabilization processes the synthesis of NPs Dobrucka ( 13). Numerous plants species have been used for synthesis of various shapes of TiO₂ NPs (Table 1). The reaction mixtures start vigorously when a precursor TiO₂ salt is adulterated with plant extract, color change indicates the first sign of synthesis that can then be confirmed afterwards by spectroscopic techniques. Several color indicators have been reported ranging from light green to dark green in the formation of TiO₂ NPs Dobrucka ( 13), Rajakumar et al. ( 23), Rajakumar et al. ( 24).

Table 1. TiO₂ nanoparticles synthesized from different plants species.

S.no	Plant taxa	Part used	Shape	Size (nm)	Characterization	Ref
1	Acanthophyllum laxiusculum Schiman-Czeika	Roots	Spherical	20–25	XRD, FTIR, EDAX and TEM	Madadi and Lotfabad ( 25)
2	Ageratina altissima (L.) R.M. King and H. Rob.	Leaves	Spherical	60–100	XRD, FTIR, and FSEM	Ganesan et al. ( 26)
3	Aloe vera (L.) Burm.f.	Leaves	Irregular	60	TEM,XRD,UV, TGA and PSA	Rao and colleagues ( 27)
		WP	Irregular	60–80	XRD, PSA, SEM and FTIR	Khadar et al. ( 28)
4	Annona squamosa L.	Peel	Polydisperse	23	XRD, SEM, TEM and EDS	Roopan and colleagues ( 29)
5	Anisomeles malabarica (L.) R.Br. ex Sims	Leaves	–	18	XRD	Saravanan et al. ( 30)
6	Azadirachta indica A.Juss.	-	Spherical	124	UV and FTIR	Sankar et al. ( 31)
7	Calotropis gigantea (L.) Dryand.	Flower	Spherical	10	SEM, EDX and XRD	Marimuthu and colleagues ( 18)
8	Catharanthus	Leaves	Cluster	25	XRD, FTIR and SEM	Velayutham and colleagues ( 32)
9	Senna auriculata (L.) Roxb.	Leaves	Spherical	38	UV, FTIR, FSEM and XRD	Valli and Geetha ( 33)
10	Cicer arietinum L.	Seeds	Spherical	14	TEM,XRD,UV and TGA	Kashale and colleagues ( 34)
11	Cinnamomum tamala (Buch.-Ham.) T. Nees and Eberm.	Leaves	–	8–20	FESEM,TEM and FTIR	Naik et al. ( 35)
12	Citrus sinensis (L.) Osbeck	Peel	Tetragonal	19	TEM, XRD, TGA and PSA	Rao et al. ( 36)
13	Curcuma longa L.	WP	–	50	AFM, SEM, XRD and UV	Jalill and colleagues ( 19)
14	Cynodon Dactylon (L.) Pers.	Leaves	Hexagonal	13–34	XRD, FTIR and SEM	Sahu et al. ( 37)
15	Dandelion	Pollen	Rod	–	XRD, FSEM and TEM	Bao and colleagues ( 21)
16	Echinacea purpurea (L.) Moench	WP	Polydisperse	120	TXRF, SEM and XRD	Dobrucka ( 13)
17	Eclipta prostrate (L.) L.	Leaves	Spherical	36–68	FTIR, XRD, AFM and FESEM	Rajakumar and colleagues ( 23)
18	Euphorbia prostrate Aiton	Leaves	Poly disperse	83.22	SAED, TEM and AFM	Zahir et al. ( 38)
19	Hibiscus rosa-sinensis L.	Flower	Spherical	–	FTIR, SEM and XRD	Kumar and colleagues ( 39)
20	Jatropha curcas L.	Latex	Spherical	25–100	SAED, EDAX, XRD and FTIR	Hudlikar and colleagues ( 40)
21	Morinda citrifolia L.	Leaves	Spherical	15–19	EDAX, FTIR, SEM and XRD	Sundrarajan and colleagues ( 41)
22	Moringa oleifera Lam.	Leaves	Spherical	100	UV and SEM	Sivaranjani and Philominathan ( 42)
23	Nyctanthes arbor-tristis L.	Leaves	Spherical	100	SEM and PSA	Sundrarajan and Gowri ( 43)
24	Ocimum basilicum L.	Leaves	Hexagonal	50	XRD, FTIR, SEM, TEM and EDAX	Jayasinghe et al. ( 44)
25	Piper betle L.	Leaves	Spherical	7	FTIR, UV, XRD, and SEM	Hunagund et al. ( 45)
26	Psidium guajava L.	Leaves	Spherical	32.58	FESEM, XRD and SEM	Santhoshkumar and colleagues ( 46)
27	Solanum trilobatum L.	-	Spherical	70	FTIR, XRD, AFM and FESEM	Rajakumar and colleagues ( 24)
28	Vigna radiate (L.) R. Wilczek	Legume	Oval	–	SEM and FTIR	Chatterjee et al. ( 47)
29	Trigonella foenum-graecum L.	Leaves	Spherical	20–90	FTIR, UV, XRD, HR-TEM and HR-SEM	Subhapriya and Gomathipriya ( 48)

WP: Whole plant.

Majority of green synthesis studies have been conducted on leaves extracts, as it is a rich source of metabolites. Spherical TiO₂ NPs resulted when Annona squamosa L. was added to the aqueous solution of TiO₂ salt at room temperature Roopan et al. ( 29). Similarly, leaf extract of Calotropis gigantea (L.) Dryand. was reported to reduce TiO₂ to nanoparticles within 6 hours. This high bio-reduction potential was ascribed to the presence of primary amines containing in the extract. The bio-mediated TiO₂ NPs showed good acaricidal activity against the larvae of Rhipicephalus microplus and Haemaphysalis bispinosa Marimuthu and colleagues ( 18). TiO₂ NPs synthesized from aqueous leaf extract of medicinally important plant Catharanthus roseus (L.) G.Don has been reported. The aliphatic alcohols and amines present in the extract contributed to synthesis of TiO₂ NPs. The particle size ranged between 25–110 nm with irregular morphologies Velayutham et al. ( 32). Bio-mediated TiO₂ NPs have also been obtained from Morinda citrifolia L. extracts. The resultant NPs were confirmed by EDX, FTIR, SEM and XRD Sundrarajan et al. ( 41). The average size revealed via SEM was 15 nm, FTIR spectral data showed the presence of anthraquinones and various phenolic compounds which are supposed to be active reactants for the reduction of TiCl₄ to TiO₂ NPs. Moringa oleifera Lam. leaf extract was used to synthesize 100 nm nanoparticles with different structures and having good wound healing potential Sivaranjani and Philominathan ( 42). TiO₂ NPs from Hibiscus rosa-sinensis L. leaf extract showed high antimicrobial activity against both gram-negative and positive strains of bacteria Kumar et al. ( 39). Nyctanthes leaves extracts derived TiO₂ NPs had uniform spherical shape and ranged in size from about 100 to 510 nm. These NPs were found to have a significant pediculocidal, acaricidal, and larvicidal activity Sundrarajan and Gowri ( 43). Cicer arietinum L. beans extract TiO₂ NPs (14 nm) have been synthesized, FTIR confirmed that the reduction is attributed to the presence of different phenolic compounds in the extract Kashale et al. ( 34). The variation in size and morphology observed among the reported studies is due to the influence of reaction temperature, time and source of plant Dobrucka ( 13), Roopan and colleagues ( 29). Thus, improvements can be established in these parameters as these aspects influence the synthesis mechanism. Furthermore, a wide propitious plant extracts are left to be explored for the synthesis of TiO₂ NPs.

2.2. Microorganism-based synthesized NPs

Many microbial species have been exploited to synthesize metallic NPs Nadeem and colleagues ( 16). TiO₂ NPs with various shapes and sizes have been reported in recent years (Table 2). Bacterial extracts in this regard have also been utilized for the green synthesis of TiO₂ NPs. Similarly, like their plant counterparts, bacterial metabolites also play a crucial role in the bio-reduction and stabilization of TiO₂ NPs. Órdenes-Aenishanslins and colleagues ( 14) reported synthesis of TiO₂ NPs by using Bacillus mycoides, spherical NPs (40–60 nm) were observed and confirmed by UV, TEM, FTIR and DLS. TiO₂ NPs (28–54 nm) synthesized using Aeromonas hydrophila extract showed effective inhibitory activity against Staphylococcus aureus (33 mm inhibition zone) and S. pyogenes (31 mm inhibition zone) Jayaseelan and colleagues ( 8). Jha et al. ( 49) observed the biosynthesis of TiO₂ NPs by the bacterium Lactobacillus and proposed that these NPs were synthesized through the combined action of oxidoreductases and glucose at mild pH. However, owing to their potential pathogenicity and laborious process bacterial synthesis have fever chances to be commercialized.

Table 2. TiO₂ nanoparticles synthesized from different microbial species.

S.no	Bacterial species	Part used	Shape	Size (nm)	Characterization
1.	Aeromonas hydrophila	Spherical	40.50	FTIR, XRD, FESEM and AFM	Jayaseelan and colleagues ( 8)
2.	Bacillus amyloliquefaciens	Spherical	22.1–97.2	FTIR, XRD, SEM and EDAX	Khan and Fulekar ( 50)
3.	Bacillus mycoides	Polydisperse	40–60	UV, TEM, DLS and FTIR	Órdenes-Aenishanslins and colleagues ( 14)
4.	Bacillus subtilis	Spherical	30–40	UV and TEM	Singh ( 20)
5.	Bacillus subtilis	Spherical	66–77	UV, XRD, FTIR, AFM and SEM	Kirthi et al. ( 51)
6.	Bacillus subtilis	Spherical	10–30	FTIR, UV, XRD and TEM.	Dhandapani et al. ( 52)
7.	Lactobacillus	Spherical	24.63	XRD and TEM	Jha and colleagues ( 49)
8.	Lactobacillus	Spherical	40–60	TEM and XRD	Prasad et al. ( 53)
9.	Planomicrobium sp.	Spherical	100	XRD, FTIR and SEM	Malarkodi et al. ( 54)
10.	Aspergillus niger	Spherical	73.58	XRD, SEM and UV	Durairaj et al. ( 55)
11.	Aspergillus tubingensis	–	<100	AFM, EDS, SEM and TEM	Babitha and Korrapati ( 56)
12.	Aspergillus flavus	Spherical,	62–74	FTIR, XRD, AFM, SEM and TEM	Rajakumar and colleagues ( 57)
13.	Fusarium oxysporum	Quasi-spherical	9.8	FTIR, TEM, XRD and XPS	Bansal et al. ( 58)
14.	Fusarium oxysporum	Spherical	10	SAED, TEM, XRD and XPS	Bansal et al. ( 59)
15.	Aspergillus niger, Rhizoctonia bataticola, Aspergillus fumigatus, and Aspergillus oryzae.			DLS, TEM, AFM	Raliya and Tarafdar ( 60)

The use of fungi in synthesis of metallic NPs has got substantial attention as they offer certain benefits over bacterial synthesis Pantidos and Horsfall ( 15). Ease of scaling up, easier extraction, large surface area and economic viability are significant advantages to consider Mukherjee et al. ( 61). Fungus mediated, TiO₂ NPs with various shapes and sizes have been reported in recent years as well (Table 2). Fungus have the intrinsic ability to reduce bulk salt to elemental or ionic state either via enzymes or metabolites (Figure 2). Extract of Aspergillus flavus was reported to have capability of reducing TiO₂ ions to TiO₂ NPs. The NPs showed good antibacterial activity against E.coli Rajakumar et al. ( 57). Saccharomyces cerevisa extract has also been used to synthesize TiO₂ NPs (12.6 nm), FTIR results confirmed that the reduction was attributed to the quinines and membranes reductases present in cells Jha and colleagues ( 49). The surface chemistry and pH of culture media also play an important role in synthesis of TiO₂ NPs. Like bacteria, fungi mediated TiO₂ NPs also have safety drawbacks. However, the application of non-pathogenic strains will wipe out the risk and could be used for commercial purposes.

Figure 2. Fungus mediated biosynthesis of TiO₂ nanoparticles.

2.3. Biological derivatives

Various biological derivatives as a green source for nanoparticle synthesis have also been utilized apart from micro and macro organisms Balasooriya et al. ( 62). However, only a few researchers have particularly explored the use of biological derivatives for biomimetic synthesis of TiO₂ nanoparticles. For instance, Farag et al. ( 63) utilized cellulose in order to synthesize TiO₂ nanoparticle having average size of 5–10 nm. The peptide R5, biological derivative of Cylindrothica fusirormis have also been exploited for the synthesis of TiO2 nanoparticles Sewell and Wright ( 64). Titanium nano wires synthesized using alpha synuclein, a protein have been reported by Padalkar et al. ( 65). Bacterial flagella were used by Li et al 2012as template for production of titanium nanotubes. The lignocellulose waste material derived from rice straw has also been utilized for the synthesis of TiO₂ nanoparticles Ramimoghadam et al. ( 66). Chen et al. ( 67) reported biomimetic synthesis to produce TiO₂ nanoparticles using different enzymes. Rutile TiO₂ nanoparticles were obtained when using glucose oxidase enzyme, catalase resulted in formation of anatase TiO₂ nanoparticles while lysozyme resulted in formation of monoclinic anatase TiO₂ nanoparticles Chen et al. ( 68). Some other notable biological derivatives used for biomimetic synthesis of TiO₂ nanoparticles are given in Table 3. In compassion with microbial-derived NPs, these derivatives based NPs are safe, cost efficient and scalable as well. Such NPs could be scaled for commercial applications including food and pharmaceuticals. Nevertheless, more studies should be carried out to address their safety/toxicity.

Table 3. TiO₂ nanoparticles synthesized from biological derivatives.

S.no	Bio-products	Shape	Size (nm)	Characterization	Ref
1.	Albumin	Spherical	50	XRD, FSEM and TEM	Bao and colleagues ( 21)
2.	Egg shell	Rod	10	TGA UV,FTIR, XRD and HRTEM	Yang et al. ( 69)
3.	Gelatin	Spherical	15	TEM, FTIR, XRD and EDAX	Bagheri et al. ( 70)
4.	Lignin cellulose	–	13	TGA,UV,FTIR, XRD and TEM	Ramimoghadam and colleagues ( 66)
5.	Starch	Irregular	64–80	XRD, UV, HRTEM and FESEM	Muniandy et al. ( 71)
6.	Arginine	Spherical		SEM TEM EDX FTIR XRD XPS	Shi et al. ( 72)
7.	Peptides	Spherical	30–70	SEM DLS EDX, XRD	Cole et al. ( 73)
8.	Polyamine	Hollow spheres	3–4	TEM XRD XPS	Yan et al. ( 74)
9.	Lysozyme		50	UV, XRD HR-TEM	KyuáKim and HyeokáPark ( 75)
10.	Pomelo Peel		90	UV-DRS, XRD, FTIR, SEM,	Zhang et al. ( 76)
11.	Protamine	Spherical	50	SEM TEM FTIR XPS	Jiang et al. ( 77)

3. Applications of green TiO₂ NPs

Green mediated NPs have many applications in various fields of physical sciences, medicine and enginneering technology Subhapriya and Gomathipriya ( 48). Though, biogenic TiO₂ NPs are studied for a lesser number of practical applications. However, results proclaim that these green synthesized NPs exhibit huge potential as compared to chemical and physical mode of synthesis. The most important application which is widely exploited is their incredible photocatalytic activity to clean contaminated water and eliminate environmental pollutants Sankar and colleagues ( 31), Pelaez et al. ( 78). It also exhibits a vast application in field of electronics, energy production, making of batteries and sensors Órdenes-Aenishanslins and colleagues ( 14), Kashale and colleagues ( 34). The biomedical potential of green mediated TiO₂ NPs have also been exploited, the main stream application includes photodynamic cancer treatment, antileshmanial agent and antimicrobial therapies Rajakumar and colleagues ( 57), Sahu and colleagues ( 37), Zahir and colleagues ( 38). The latter sections of the present review highlights, the most exploited biomedical applications with mechanistic approaches.

3.1. Antimicrobial potential

In literature, different metallic NPs have been used against various strains of bacteria Nadeem and colleagues ( 16). Similarly, TiO₂ NPs also exhibit eco-friendly biocidal properties, which are attributed to their strong oxidizing potential. These NPs have been used against a wide range of infectious microbes including various bacterial strains, endospores, fungi, algae, protozoa, viruses, microbial toxins and prions Visai et al. ( 79). TiO₂ NPs trigger the onset of reactive oxygen species (ROS) when confronted with microbial cells Jayaseelan and colleagues ( 8). These ROS kill microbes by disrupting cell wall’s integrity mainly by phospholipids oxidation, which results in reduced adhesion and distorted ionic balance. Inside the cytosol, it inhibits the respiratory cytosolic enzymes and modifying macromolecules structures, producing substantial effects on cellular integrity and gene expression. Furthermore, it also decreases the phosphate uptake and cellular communication across the cell Jayaseelan and colleagues ( 8), Kubacka et al. ( 80). A possible mechanism of action is described in Figure 3.

Figure 3. Mechanistic representation of TiO₂ nanoparticles effect on bacterial cell.

Both green synthesized and chemically derived TiO₂ NPs kill microbes in same fashion but the biologically derived NPs show better antibacterial activity. Their excellent antimicrobial potential is attributed to the capping agents provided by the plant extracts Kumar and colleagues ( 39). Morphology of NPs, membrane biochemistry and type of bacteria significantly affect antibacterial activity. Green synthesized TiO₂ NPs can efficiently inhibit both gram-positive and gram-negative bacteria, but due to comparative structural complexity of gram-negative bacterial cell wall, it is more reactive against gram-positive bacteria Marimuthu and colleagues ( 18). Some other studies of bio-mediated TiO₂ NPs tested against various stains of pathogens are presented in Table 4. The antimicrobial activity of bio-mediated TiO₂ NPs can be enhanced if irradiated with UV and fluorescent light Jayaseelan and colleagues ( 8), Roopan and colleagues ( 29). TiO₂ NPs Nano composites also exhibit enhanced antileshmanial activity, when green synthesized TiO₂ NPs were applied to Leishmanial cultures; lower cell viability, stunted growth and DNA fragmentation was observed Kubacka and colleagues ( 80). When compared to standard antibiotic disk TiO₂ NPs showed better antimicrobial activity Santhoshkumar and colleagues ( 46). Thus with such improved antimicrobial activity it considerably diminishes the occurrences for the development of antibiotic confrontation of pathogenic stains.

Table 4. TiO₂ nanoparticles synthesized from different microbial species.

S.No	Source of synthesis	Microbes tested	Method used	Ref
1.	Aspergillus flavus	Shigella dysenteriae type I, Staphylococcus aureus, Citrobacter sp., Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Candida albicans and F. oxysporum	Agar diffusion	Rajakumar and colleagues ( 57)
2.	Planomicrobium sp.	Bacillus subtilis, Klebsiella planticola	Agar plate	Malarkodi and colleagues ( 54)
3.	Bacillus subtilis	E. coli	Luria broth agar	Singh ( 20)
4.	Aeromonas hydrophila	A. hydrophila, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis	Disk diffusion	Jayaseelan and colleagues ( 8)
5.	Euphorbia prostrata	Leishmania donovani	RPMI 1640 medium	Zahir and colleagues ( 38)
6.	Hibiscus rosa-sinensis L	Vibrio cholerae, Pseudomonas aeruginosa and Staphylococcus aureus	Mueller Hinton agar	Kumar and colleagues ( 39)
7.	M. citrifolia	Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger	Agar diffusion	Sundrarajan and colleagues ( 41)
8.	Curcuma longa	F. graminearum	PDA medium	Jalill and colleagues ( 19)
9.	Psidium guajava	Staphylococcus aureus and Escherichia coli	Disk diffusion	Santhoshkumar and colleagues ( 46)
10.	Vigna radiate	E. coli, Staphylococcus aureus, Serratia marcescens, Salmonella ., Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter., Proteus mirabilis, and Shigella	Well-diffusion	Chatterjee and colleagues ( 47)
11.	Cynodon Dactylon	E. coli	Disk diffusion	Sahu and colleagues ( 37)
12.	Trigonella foenum-graecum	Staphylococcus aureus, Enterococcus faecalis, Klebsiella pneumoniae, Streptococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Bacillus subtilis, Yersinia enterocolitica and Candida albicans	Disk diffusion	Subhapriya and Gomathipriya ( 48)

3.2. Anti-parasitic activities

Metallic nanoparticles have been effectively used against many species of parasitic larva and adult’s insects Benelli et al. ( 81). Green synthesized TiO₂ NPs have also been found to be effective larvicidal agents against various species of parasitic insects as shown in Table 5. The subcellular events leading to death include decrease in the biochemical parameters involved in growth and development Durairaj and colleagues ( 55) (Figure 4). To date less has been revealed regarding the antiparasitic potential of TiO₂. However, it shows huge potential in making anti-insect lotions and ointments and many others features, which will be unveiled as the technology emerges.

Figure 4. Effect of biogenic TiO₂ NPs on larva’s biochemical factors.

Table 5. List of larva species tested against TiO₂ NPs.

S.no	Organism used	Parasites tested	Results	Ref
1.	Catharanthus	H. maculate and B. ovis	LD50 = 7.09 and 6.56 mg/L	Velayutham and colleagues ( 32)
2.	Calotropis gigantea (L.)	Rhipicephalus microplus and Haemaphysalis bispinosa	LC50 = 24.63 and 5.43 mg/L	Marimuthu and colleagues ( 18)
3.	Solanum trilobatum L.	Diculus humanus capitis, Hyalomma anatolicum and Anopheles subpictus	LC50 = 28.80,24.01, and 1.94 mg/L	Rajakumar and colleagues ( 24)
4.	Aspergillus niger	Aedes aegypti	LC50.90 8.4 and 14.9 mg/L	Durairaj and colleagues ( 55)

3.3. Photocatalytic activity

Industrial and domestic effluents contain many hazardous pollutants such as toxic dyes and nitroarene compounds. Their low solubility and high stability makes them highly persistent and resulting in many threats to aquatic life Valentín et al. ( 82). Recently, the distinctive structures and high catalytic potential of metallic NPs have been exploited. Their large surface area makes them excellent heterogeneous catalysts Rodrigues et al. ( 83). Moreover, these nanostructure catalysts can be easily recovered and recycled reaction mixture. But the agglomeration and toxicity of these metallic nanoparticles remain a concern Hotze et al. ( 84), Park et al. ( 85). TiO₂ NPs have been used mostly in catalyzing various reactions, due to their benign properties, low toxicity, high stability, excellent photocatalytic potential and optical properties Shah et al. ( 86). The photocatalytic activity of green mediated TiO₂ NPs have been reported by various authors for reduction of various dyes and compounds Valencia and colleagues ( 6), Bao and colleagues ( 21), Sankar and colleagues ( 31), Muniandy and colleagues ( 71), KyuáKim and HyeokáPark ( 75), Pelaez and colleagues ( 78). Figure 5 shows a typical pathway of electron flow after the possible photo excitation. The photo excited electron initiates a cascade of electron transfer chain which results in degradation of toxic compounds aided by oxidizing potential of phytochemicals of the extracts Ganesan and colleagues ( 26), Muniandy and colleagues ( 71), Pelaez and colleagues ( 78). When compared with chemical synthesized TiO₂, the green mediated NPs showed excellent photocatalytic potential. The reducing ability is dependent on plant species, type of dye and temperature Zahir and colleagues ( 38). For instance when doped with other NPs and composites it significantly improve the catalytic potential. Salomatina et al. ( 87). TiO₂ NPs exhibit an incredible photocatalytic activity as revealed by these results, but still the reducing phenomenon is not elucidated completely which must be assessed.

Figure 5. Photocatalytic mechanism of biogenic TiO₂ NPs under light source.

Conclusion

Nanostructures materials have triggered a considerable attention in every field of science. Though metallic nanoparticles are produced by physio chemical process, but their toxicity, cost and laborious synthesis have led scientists to devolop new approaches for designing nanostructures. The solution of this dilemma resulted in an easy, safe and scalable approach known as the green synthesis method. In this method a precursor metallic salts is reduced by the metabolites of the organism. Moreover, NPs with high yield and better morphologies are also obtained. In this review article, we have discussed the synthesis of titanium oxide nanoparticles from different biological sources (plants, microbes and related bio-products). Furthermore the applications of green mediated titanium oxide NPs have also been described. Though, Titanium NPs have been reported by many authors till now but the synthesis steps have to be better characterized and need to be elaborated further by the identification of the responsible compounds in the extracts, the optimization of different factors such as pH, temperature or the amount of precursor salt, and extract should be studied for optimal yield and stable NPs production at feasible commercial scale.

Disclosure statement

No potential conflict of interest was reported by the authors.

Notes on contributors

Muhammad Nadeem is an MPhil graduate scholar from Quaid I Azam University Islamabad, Pakistan. His research interests includes nanoparticle synthesis and their potential applications and toxicity.

Duangjai Tungmunnithum is a research scientist with expertise in biochemistry, medicinal chemistry and phytochemistry.

Christophe Hano is a senior research scientist. His research area includes medicinal plants biotechnology, plants physiology and nanoparticles synthesis.

Bilal Haider Abbasi is a senior scientist. His area of research includes bioprocess technology, medicinal plants biotechnology and green synthesis of nanoparticles.

Syed Salman Hashmi is an MPhil research Scholar at Quaid I Azam University Islamabad Pakistan. His current research is focused on the green synthesis of nanoparticles and its biological applications.

Waqar Ahmad is an MPhil research Scholar at Quaid i Azam University Islamabad Pakistan. His current research is focused on the green synthesis of nanoparticles and interactions with plants.

Adnan Zahir is an MPhil research Scholar at Quaid i Azam University Islamabad Pakistan. Presently he is working on biosynthesis of metallic nanoparticles and plant tissue culture.

ORCID

Muhammad Nadeem http://orcid.org/0000-0002-0373-5366

Christophe Hano http://orcid.org/0000-0001-9938-0151

Bilal Haider Abbasi http://orcid.org/0000-0002-6529-2134

Notes

Abbreviations: EDAX: energy dispersive X-ray; FESEM: field emission scanning electron microscope; FTIR: Fourier-transform infrared spectroscopy; SAED: selected area (electron) diffraction; SEM: Scanning electron microscopy; TEM: transmission electron microscopy; TGA: thermo gravimetric analysis; UV: Ultraviolet; XRD: X-ray powder diffraction