Green synthesis of copper oxide nanoparticles for biomedical application and environmental remediation.

Recent development in nanoscience and nanotechnology has contributed to the wide applications of metal and metal oxides nanoparticles in several field of sciences, research institutes and industries. Among all metal oxides, copper oxide nanoparticles (CuONPs) has gained more attention due to its distinctive properties and applications. The high cost of reagents, equipment and environmental hazards associated with the physical and chemical methods of synthesizing CuONPs has been a major setback. In order to puffer solution to the aforementioned challenges by reducing environmental pollution and production of cheaper nanoparticles with good properties and efficiency, this review focus on collection of comprehensive information from recent developments in the synthesis, characterization and applications from previous scientific findings on biological method of synthesizing CuONPs due to the acclaimed advantages of been cheap, environmentally friendly, convenient and possibility of been scale up in into large scale production reported by numerous researchers. Our finding also support the synthesis of CuONPs from plant sources due to relative abundance of plants for the production of reducing and stabilizing agents required for CuONPs synthesis, potential efficiency of plant biomolecules in enhancing the toxicity effect of CuONPs against microbes, prevention of environmental pollution due of nontoxic chemicals and degradation effectiveness of CuONPs synthesized from plant sources. Furthermore, this study provide useful information on the rapid synthesis of CuONPs with desired properties from plant extracts.

Introduction

Since few decades ago, the advance in nanoparticles technology have played a remarkable role in medical, pharmaceutical and textile industries. Metal nanoparticles like silver, zinc and gold have been used as therapeutic agents in medical institutes for some years [1, 2, 3, 4]. Transitional metal oxides such as CuO, TiO2, Fe3O4, ZnO, and NiO NPs have shown effective applications as advanced nano-substances in energy, biomedical and environment fields of study. The strong adsorption capability exhibited by these NPs significantly enhance their performance and applications [5]. The investigation of the biological properties of metal nanoparticles have been on an increase. Recently, several researchers had embarked on the assessment of the biological activities of metal oxide nanoparticles such copper oxide from which improved biological and photocatalytic activities better than those obtained from metal nanoparticles have been reported [6, 7, 8, 9, 10]. The probable applications of copper oxide nanoparticles (CuONPs) in gas sensors, waste treatment, catalysis, batteries, food preservation, high temperature superconductors, solar energy conversion, photovoltaic devices, dye removal, field emission emitters and in agriculture have been established [11, 12, 13, 14]. Aside the previously mentioned usage, CuONPs showed exclusive anticancer, antimicrobial and antioxidant efficacy which renders them a promising tool for biomedical applications [15, 16]. Different physical and chemical approaches like microwave irradiation, thermal decomposition, sol gel, colloidal thermal synthesis, sonochemical, hydrothermal, and quick precipitation have been reported for the synthesis of CuONPs with desired morphologies qualities [17]. However, these methods require labour-intensiveness, energy, intensive routes, expensive and hazardous chemicals [18]. Henceforth, developing novel biocompatible approaches that can help to overcome the cited limitations is of high necessity in nanomaterials synthesis [19]. Records have shown that there are increase in the shift from the physical and chemical method of synthesizing metal and metal oxide nanoparticles to the biological method termed biosynthesis or green synthesis of nanoparticles [20, 21]. The biological approach of metal or metal oxide nanoparticle synthesis focus on the utilization of bacteria, fungi, algae, yeast and plant extracts, as reducing agent for the synthesis of nanoparticles which support biocompatibility and large scale production [22, 23]. The phyto-synthesis of CuoNPs have gained more attention recently owing to its sustainability, cost effectiveness and simplicity [24]. This review focused on provision of scientific findings that could help in limiting the shortcomings of both the physical and chemical method of CuONPs from recent findings on the method of synthesis, characterization techniques and some applications of CuONPs synthesized using plants sources.

Synthesis of Cu-NPs

Many researchers have reported various approaches of synthesizing CuONPs, among which we have ultrasound irradiation hydrothermal, biosynthesis approaches, electron beam lithography, solid-state reaction, sol-gel, template methods using surfactants, microwave-assisted protocol, decomposition of copper acetate and sonochemical synthesis [25, 26, 27, 28, 29, 30, 31]. It has also been reported that method of CuONPs synthesis affect their morphological properties and toxicity behaviour [29]. The flow chat representing the various methods of CuONPs synthesis is showed in Figure 1.

Figure 1

Flow chat representing the various methods of synthesis of CuONPs

Chemical approach

This approach entail the use of some chemicals/regents for the reduction of copper ions during the synthesis of CuONPs [33]. Chemical approach of nanoparticles formation is grouped into two forms; green chemical approach and traditional approach. For the green chemical approach, chemicals synthesized from organic material such as ascorbic acid are used while inorganic compounds such as sodium borohydride and potassium borohydride are used in the traditional approach. The use of ascorbic acid as a reducing agent for the synthesis of CuONPs has been reported [34] the use of potassium borohydride in formation of CuONPs has also be established [35]. Several reports had shown that large energy consumption, environmental pollution, the use of high pressure and temperature, expensive and toxic chemicals as huge limitations of chemical method of synthesizing CuONPs and other transitional metal oxide NPs [36, 37].

Physical method

This method make use of electric current as source of electron in the generation of required electron during CuONPs synthesis [38]. The rampantly used techniques in the physical approach of CuONPs synthesis are electro-spraying, laser pyrolysis, laser ablation and evaporation-condensation. Among the physical approach, pulsed laser induced ablation technique had gained more attention owing to the fact that it’s easy, eco-friendly and uniformly nanoparticles are obtainable [39]. In the synthesis of CuONPs via laser ablation, high power pulsed laser is the cogent and essential requirement for ablation on the surface of the sample [40].The variation of some parameters such as pulse width, wavelength, repetition rate of laser source, ablation time and temperature allows the formation of nanoparticles of desired morphological identities [41]. The advantages of the physical method are production of CuONPs with uniform, controlled sized and high purity [42]. Despite the evident advantages, the cost infectiveness, operation skills, high power and energy required offer great set back to the physical method of synthesizing CuONPs.

Biological approach synthesis

The biological approach of nanoparticles synthesis encompasses the utilization of organisms (bacteria yeast and fungi) and extract from various parts of plant as reducing agent of the metal ions [43, 44, 45]. The biosynthesis of CuONPs using the following bacteria Phormidium cyanobacterium [46], Morganella morganii [47], Serratia sp [48] and Escherichia coli [47] had been reported.

Despite the ecofriendly advantage of synthesizing nanoparticles from microorganism the following are their limitations; toxicity of some bacterial, difficulties in isolation and incubation process [49]. Nevertheless, plants remains the only ideal potential for metal and metal oxide nanoparticles, this plausibility is attributed to rapid reaction rate with low energy, occurrence of several biomolecules, cost effectiveness, good stability, absence of hazardous chemicals, safe and easy operation procedures [50]. Biomolecules found in plant extracts function as both reducing and stabilizing agents during the synthesis of CuONPs and other metal nanoparticles [51, 52, 53]. Biomolecules such as flavonoids, proteins, tannins, phenols and terpenoids have been reported as good reducing and stabilizing agents for CuONPs synthesis [54]. Examples of plants that have been used for the synthesis of CuONPs are listed in Tables 1 and 2.

Table 1

Characterization techniques for synthesized CuONPs.

S/N	Techniques	Properties	Parameters	Ref
1	UV visible spectroscopy	NP formation	Confirmation for the synthesis	[104]
2	Scanning tunneling microscope	Size and morphology analysis	Topology and chemical analysis	[105]
3	Atomic force microscope	Size and morphology analysis	Size, morphology, surface roughness and texture	[106]
4	Scanning electron microscope	Size and morphology analysis	Topology, size, morphology, crystallographic structure and composition	[107]
5	Dynamic light scattering	Size and morphology analysis	Amorphous contents and polymorphism	[83]
6	Transmission electron microscope	Size and morphology analysis	Topology, size, morphology and crystallographic structure	[108]
7	Differential scanning calorimetry	Thermal analysis	Amorphous contents and polymorphism	[83]
8	Fourier transmission infrared spectroscopy	Optical characterization and Functional group analysis	Identification of functional groups	[109]
9	Zeta potential	Surface analysis	Colloidal stability and surface charge	[110]
10	Energy dispersive X-ray	Elemental analysis	Chemical composition and purity	[111]
11	X-ray fluorescence spectroscopy	Elemental analysis	Chemical composition and thickness of coating	[112]
12	X-ray absorption spectrometry	Elemental analysis	Electronic structure and elemental composition	[113]
13	Particle size analysis (PSA)	size analysis	To measure the distribution of size	[114]

Table 2

Advantages and disadvantages of different methods of CuONPs synthesis.

Methods	Advantages	Disadvantages	Ref
Chemical	It enhance large scale production.	Generation of non-ecofriendly products, it energy intensive processes, use of toxic solvents as reducing and stabilizing agents.	[55, 56, 57]
physical	Control crystallinity, shape and production of CuONPs with uniform, controlled sized and high purity are achievable	require high capital costs and consume high energy	[58, 59]
Biological	This method is cost effectiveness, non-use of toxic materials and simple	using microorganisms is non-attractive due to the requirement of aseptic cultivation and increased production costs at industrial scale	[60, 61, 62]

Advantages and disadvantages of different methods of n class="Chemical">CuONPs synthesis.

Some advantages and disadvantages of the methods used in the synthesis of CuONPs are presented in Table 3.

Table 3

SPR bands, and functional groups, characterization techniques of biosynthesized CuONPs from some plant sources.

S/N	Plants name	Plants parts	SPR peak (nm)	Functional group prediction		Techniques for Morphological Assessment	Shape	Size	Ref.
1	Eupatorium odoratum	Leaf	301	3976	O–H	UV, FTIR, XRD, TEM	spherical	-	[115]
				2936	C–H
				1618	C=O
2	Acanthospermum hispidum	Leaf	305	3406	O–H	UV, FTIR, XRD, TEM	spherical	-	[115]
				2838	C–H
				1520	C=C
3	Hylotelephium telephium	Flower	350	3388	O–H	UV, FTIR, SEM, TEM, XRD,EDX	spherical	83	[116]
				1980	C=O
4	Kalopanax pictus	Leaf	368	3,467	N–H	UV, FTIR, SEM, TEM, EDX, XPS	spherical	26–67	[117]
				1,584	C=C
				1,360	C–N
5	Pterolobium hexapetalum	Leaf	274	3420	O–H	XUV, FTIR, RD, TEM, and EDX	spherical	10–50	[118]
				2915	C–H
				1625	C=C
6	Coriandrum sativum L	Seed	-	-	-	XRD,FESEM,DLS	Irregular	18.2	[119]
7	Oak	Fruit	-	3415	O–H	UV,FTIR, FESEM,XRD	quasi-cubic	34	[120]
				1654	C=O
8	Albizia lebbeck	Leaf	413			SEM, EDS, UV,XRD, TEM	spherical	100	[121]
9	Eichhornia crassipes	Leaf	310	3314	O–H	UV, FTIR, FESEM, TEM, EDX	spherical	15–30	[122]
				1624	N–H
				1217	C–O–C
10	Citrofortunella microcarpa	Leaf	305	3000–3350		UV, FTIR, XRD, SEM and FTIR. EDS	spherical	54–68	[123]
				820–880	C–H
				1357	C=O
11	Verbascum thapsus	Leaf	350	3442	O–H	UV, FTIR, XRD, SEM, FTIR	spherical	-	[124]
				2922	C–H
				1616	C=O
12	Euphorbia pulcherrima	Flower	240	3384	O–H	FTIR, XRD, HRTEM	cubic	19.2	[25]
				1595	C=O
13	Sida Rhombifolia	Leaf	471	3439		UV, FTIR, XRD, FESEM	spherical	10	[125]
				1658
14	Seidlitzia rosmarinus	Bark ashes	385	3346	O–H	UV, FTIR, XRD, FESEM		26	[126]
				2900	C–H
				1500	C=O
15	Enicostemma axillare (Lam.)	Leaf	264	-	-	UV, XRD, EDS, SEM, TEM		30	[69]
16	Terminalia catappa L.	Leaf	372	3209	O–H	UV, XRD, FTIR, SEM, TEM	spherical	103–29	[127]
				2920	C–H
				1557	C=O
17	Punica granatum	Fruits Peel	282	3379	O–H	UV, XRD, FTIR, SEM	spherical	10–100	[128]
				1577	C=O
18	O. cochinchinense	Leaf		3323	O–H	UV, XRD, FTIR, SEM,SEAD	-	-	[129]
				1550	C=C
				1338	C–N
19	Rosa canina	Fruit	262	3550–3200	O–H	UV, XRD, FTIR, FESEM, WDX, EDX, TEM	spherical	15–25	[130]
				1670	C=O
				1405	C=C
20	Aloe barbadensis	Leaf	285	3405	O–H	UV–Vis, PL, FT-IR, XRD, SEM,TEM	spherical	15–30	[131]
				1538	C=C
				944	C–C
21	Sambucus nigra	Fruit	278	3300–3500	O–H	UV, XRD, FTIR,	-	-	[132]
				2299	C–H
				1621	C=C
22	Calotropis procera	Leaf	355	3414	O–H	UV, XRD, FTIR,SEM	cylindrical	46	[133]
				2923	C–H
				1598	C=C

X-ray photo electron spectroscopy XPS, Selected Area Electron Diffraction (SAED) wavelength-dispersive X-ray spectroscopy (WDX).

X-ray photo electron spectroscopy XPS, Selected Area Electron Diffraction (SAED) wavelength-dispersive X-ray spectn class="Chemical">roscopy (WDX).

Formation mechanism for the synthesis of CuONPs from plant extracts

Green synthesis of CuONPs using plant extracts as the source of electron generation for the reduction of copper salt display some advantages over the use of microbes because it does not require cell culture maintenance and it can be scaled up for large-scale synthesis. The formation of CuONPs occurs with an observable change in the color of the extract when copper salt was added. Several studies have revealed that the phytochemicals in the plant extracts first form complexes with the iron salts and then reduce the ions to form nanoparticles. The biomolecules in the plants extracts usually react with copper ion to cause reduction which subsequently transform into CuONPs [63, 64].

The probable mechanism involved in the synthesis of CuONPs is represented with the following equations.

Effects of experimental parameters on CuONPs synthesis

Effect of pH

pH value helps in the determination of the level of acidity and basicity on a solution. Report had shown the influence of varying pH value on the synthesis CuONPs and other metallic oxide nanoparticles. Significant influence of pH on size and texture of some nanoparticles biosynthesized from plant extracts have been reported [65]. Also, variation of the pH value have been adopted in controlling the shape and size of the synthesized nanoparticles [66]. Solution medium with pH values ranging from 7 to 9 has been considered as the optimum condition for the synthesis of nanoparticles from Aeromonas hydrophila extract [67].

Effect of type of plant extracts and concentrations

The synthesis of CuONPs using plants extract depend majorly on types of biomolecules found in plant extracts and the volume used [68]. The volume of plant extracts used in the synthesis of nanoparticles influence the duration of synthesis. Previous study had shown that the higher volume of extract used, the faster the rate of synthesis because more chemical constituents are available in the solution which bind with the precursor to effect rapid bio-reduction and stabilization of nanoparticles [69]. To attain an optimum condition for the green synthesis of CuONPs the ratio of the volume of plant extract must correspond to the concentration of copper precursor used [70]. The yield of CuONPs depend largely on the volume of extract used for synthesis [71]. Findings have proved that volume and kind of extract used for synthesis of nanoparticles have huge influence on their morphological properties and biological activities [72].

Time

The incubation time of nanoparticles synthesized using plant extract has been examined to influence the morphological properties and qualities of nanoparticles [73]. Other factors such as storage conditions and exposure to light also affect the reaction time of CuONPs. Long time incubation period has been stated to cause aggregation and shrinkage of particles [74].

Effect of temperature

Temperature have been considered as one of the crucial parameters that influences the synthesis of metallic oxide nanoparticles. The temperature recommended for the synthesis of CuONPs and other metallic oxide nanoparticles using plant extracts is in the range of 25–100 °C [75]. However, the synthesis of CuONPs at room temperature is more rampant due to the volatility of some secondary metabolites found in plants extracts. The effect of temperature of reaction solution on the morphological identity of nanoparticles has been reported [75]. Findings from the green synthesis of metallic oxides from plant extracts have shown rapid and complete synthesis at higher temperatures. However, higher temperature has been reported to cause poor synthesis of nanoparticles due to inactivation of biomolecules liable for the reduction of the iron precursor [76].

Characterization of CuONPs

Since the applications of CuONPs depend largely on their properties, the need for their characterization therefore remain essential. The important characterization techniques used for determining the properties synthesized CuONPs are discussed below;

UV-visible (UV-Vis) spectroscopy

UV-visible spectroscopy is a molecular spectroscopy that is based on Bouguer Lambert Beer law principle for its operation. This technique measures the Plasmon resonance and total oscillations of conduction band of electrons in conjunction with electromagnetic waves. It is also used for absorption measurements of fluids and several other materials [77]. In UV-visible spectroscopy analysis, a beam of light splits in two in which 50% of beams analysis the compound or solution in the transparent cell and the other 50% of the beam analysis the reference material parts. In the cause of the analysis, the solution absorbs light at a specific wavelengths, this wavelength is referred to as the surface plasmon resonance (SPR) of the material analyzed [77]. For CuONPs, the surface plasmon resonance is in the range of 200–350nm [78]. Findings has demonstrated that the type of extract, pH, temperature and method of synthesis affect the SPR of CuONPs which further influence it morphological properties [79, 80]. UV-visible spectroscopy reveals crucial information about the size, structure, stability and aggregation of the CuONPs [81]. Findings on detailed application of UV as characterization tools in green synthesis of CuONPs are summarized in Table 2.

FTIR spectrophotometer

FTIR spectrophotometer operates in long wavelengths in order to identify different functional groups associated with NPs. The FTIR spectral reveals functional groups present in extract containing NPs [82]. At a specific resonant frequencies, the incident light from FTIR will cause an absorption when it come in contact with a vibration frequency of the group or bond corresponding to the same frequency. The shape of molecular potential energy, vibronic coupling and mass of an atoms are accountable for absorption of particular energy. The observed differences in the FTIR spectrum of different compound or molecule is traceable to the unique arrangement of atoms [83]. The peaks corresponding to O–H, C=O, C–N, C–H, C=C are the prominent peaks associated with CuONPs. Several scientific findings had ascribed the absorption at 3000–3350 cm−1 to N–H of amine or O–H of alcohol/phenol [84]. Absorption peaks in the range of 820–880 cm−1 have been attributed to aromatic C–H bending [84]. A strong absorption peak at wavelength 2900-3000 cm−1 was credited to C–H [85]. The absorption band observed at wavelength 1600–700 are traceable to CuO [86]. The absorption band at 1600–1790 are linked to –C=O of carbonyl [87]. Reports on the comprehensive applications of FTIR in green synthesis of CuONPs are summarized in Table 2.

Size and morphological analysis

Size and morphological behavior are the most important parameters to investigate in nanoparticles because they influence the usefulness of CuONPs. The characterization equipment and techniques popularly used for size and morphology analysis are discussed as follows;

Scanning tunneling microscopy (STM)

This technique gives comprehensive information about the surface of CuONPs [88]. It is used for size estimation, morphological study and topography. It equally offers the advantages of wide range application for all forms of metals and semiconductor [88]. Quantum tunneling is the working principle guiding STM, Images are produced as variation of tunneling current tip causes movement across the surface. The growth of CuONPs has been measured with STM.

Atomic force microscopy (AFM)

AFM is used for the estimation of morphological properties such as size, roughness surface and texture [89]. AFM is different from other electron microscopes techniques because it is only used for the 3D characterization of NPs. It is capable of generating information about the geometry and magnetic behavior of nanoparticles. However, its scanning speed is slow compared to other microscopic techniques, it also produce in accurate topography especially when the probe is not dull [90]. Several morphological evaluation of biosynthesized CuONPs via AFM are showed in Table 2.

Transmission electron microscopy (TEM)

TEM is regarded as the best among other electron microscopy techniques for the determination of morphological identities of CuONPs and other metal nanoparticles [91]. In TEM technique beams of energetic electrons are transmitted through an ultra-thin sample and interfaces from which a picture is shaped [92]. The improved form of TEM with higher resolution that allows imaging of the crystallographic structure at nuclear scale is termed high resolution transmission electron microscopy (HRTEM) [93]. Reports obtained from the morphological evaluation of biosynthesized CuONPs using TEM and HRTEM are represented in Table 2.

Scanning electron microscopy (SEM)

SEM is used for morphological characterization of CuONPs. It is limited in some morphological analysis because it produces limited information regarding the true population and average size distribution [94]. SEM has been reported to damage some nanopolymer. Therefore, for an effective morphological analysis using SEM, the NPs must be capable of withstand vacuum pressure [95]. Another retrogression about this technique is that it very expensive and slow. Other results showing the morphological characterization of biosynthesized CuONPs via SEM are represented in Table 2.

Dynamic light scattering (DLS)

DLS is sometimes referred to as quasi-elastic light scattering. It performs the function of size determination and aggregation of NPs [96]. This technique is very fast, sensitive and can estimate the size of a particle on both nano and macro scale but it also have some limitation because the size of an individual particle cannot be obtained from an aggregate. The speed of DLS is dependent on particle size; small particles are very fast and vice versa [83]. Other results in which DLS has been used as characterization tools for biosynthesized CuONPs are showed in Table 2.

Energy dispersive X-ray (EDX)

EDX is used for the qualitative and quantitative identification of the elemental composition of CuONPs and several metal nanoparticles. When the beam of electrons from EDX bombard CuONPs, X-rays are emitted [97]. The emitted X-rays are analyzed qualitatively and quantitatively. For quantitative analysis, the concentration of specific element in the CuONPs are measured by the intensities of peaks while the positions of each X-ray peaks on the EDX spectrum are identified for qualitative analysis [98]. Modern technology enhance the attachment of EDX with SEM and TEM for identification and quantification of trace elements. EDX is capable of quantify elements with atomic number in the range of 4–92 [83]. Previous studies on the use of EDX as characterization tools in CuONPs biosynthesis are showed in Table 2.

X-Ray diffractometer (XRD)

XRD is used for structural and crystallinity analysis of synthesized CuONPs [99, 100]. X-ray diffraction analysis have revealed that CuONPs is a face-centered cubic phase in agreement with standard powder diffraction card JCPD file No. 48–1548. The average crystallite size of CuONPs are estimated using Debye Scherrer formula [101].D = 0:9λ/βcosθwhere d = size of Cu-NPs (nm), λ = X-ray wavelength, β = full width at half maximum of the diffraction peak and θ = measured Bragg angle. The diffraction peaks at 2θ value of 31.6°, 45.4°, 56.4°, 66.3° and 75.2° that indexed planes (110), (112), (202), (220) and (004), respectively, was used to characterize the monoclinic structure of CuONPs [102, 103]. Several findings on the structural and crystallinity analysis of biosynthesized CuONPs using XRD are represented in Table 2.

Furthermore, some researchers have adopted other techniques for the characterization of biosynthesis CuONPs. Summary of such findings are documented in Table 1.

Applications of CuONPs

CuONPs synthesized using plant extracts have been reported to exhibit numerous applications in many fields. Some applications of n class="Chemical">CuONPs are discussed below as showed in Figure 2.

Figure 2

Flow chart showing some applications of CuONPs.

Antibacterial application

The inhibitory antibacterial potential exhibited by biosynthesized CuONPs against both gram-positive and gram-negative bacterial strains had been studied [134]. The antibacterial activities of phytosynthesized CuONPs from the extract of Tecoma castanifolia leaf displayed reliable bactericidal activity that may be useful in biomedical applications [135]. Previous study have shown that the biomolecules of plant extracts used in CuONPs synthesis promote greater antibacterial efficacy against Gram-positive and Gram-negative bacterial strains. The increase in the antibacterial efficacy of CuONPs has been linked with the biomolecule (terpenoids) found in the extract during the capping process [136] The antibacterial analysis of CuONPs obtained from the agar well diffusion technique against both gram positive bacteria (Streptococcus mutans and Staphylococcus aureus) and gram negative (Pseudomonas aeroginos, Klebsiella pneumonia and Escherichia coli) showed the toxicity of CuONPs in destroying the growth of tested pathogens. The bactericidal effectiveness of CuONPs has been traced to the development of highly reactive oxygen species such as (OH, H2O2 and O2) on the surface of the CuONPs which causes the death to the bacteria [125]. Reports on the antibacterial activities of CuONPs are summarized in Table 4.

Table 4

Applications of CuONPs synthesized from plants extracts.

S/N	Plants name	Plants part	Salt	Applications	Activities	Ref
1	Eupatorium odoratum	Leaf	copper sulphate	Antibacterial	12–30 mm	[115]
2	Aloe barbadensis Miller	Leaf	Copper sulphate	Degradation antibacterial activity	98.89% maximum removal of removal of hazardous dye methylene blue.	[158]
3	Rheum palmatum L.	Root	Copper chloride	catalytic activity	Five times efficient catalyst reduction of methylene blue and rhodamine B without decrease in catalytic activity.	[159]
4	Tea	Leaf	Copper nitrate	antibacterial activity	Showed remarkable antibacterial activity against K. pneumoniae and V. cholerae with inhibition zones of 10.5 at 200Ng/disc	[160]
5	Eucalyptus globulus	Leaf	copper sulphate	Anticancer	cell cycle disruption and upregulation of pro-apoptotic genes in MCF-7 cells	[161]
6	Eucalyptus globulus	Leaf	copper sulphate	Antibacterial	Potential ROS generation for interruption of bacterial cells	[145]
7	T. arjuna	bark	Copper nitrate	catalytic activity	effective degradation of methyl blue dye	[162]
8	Camellia sinensis	Leaf	cupric acetate	Anticancer	remarkable cytotoxic effect of 50% mortality at 50 μg/ml against breast cancer cell line (MCF-7)	[17]
9.	Cistus incanus	Leaf	copper nitrate	oxidative stress	improved in conditions of oxidative stress	[163]
10.	Cissus quadrangularis	Leaf	Copper acetate	Antifungal	86% and 85% inhibition against A. niger and A. flavus at 1000 ppm	[164]
11.	Aloe Vera	Leaf	Copper sulphate	solarphotocatalytic activities	fast degradation of methylene blue in aqueous solution at room temperature under solar simulator irradiation.	[155]
12	Coleus aromaticus	Leaf	Copper sulphate	Anticancer	It offered an efficient platform for intracellular miRNA delivery and improving therapeutic outcomes for lung cancer	[165]
13	Azadirachta indica	Leaf	Copper acetate	anticancer activity	cytotoxicity against the tested cancer cell lines without affect the human cell	[166]
14	Hibiscus rosa-sinensis	Leaf	Copper acetate	anticancer activity	Great cytotoxicity against the tested cancer cell lines	[166]
15	Murraya koenigii	Leaf	Copper acetate	anticancer activity	High cytotoxicity against the tested cancer cell lines without affect the human cell	[166]
16	Moringa oleifera	Leaf	Copper acetate	antioxidant	Efficient antioxidant potency	[166]
17	Tamarindus indica	Leaf	Copper acetate	antioxidant	promising antioxidant potency	[166]
18	Euphorbia maculata	Aerial part	Copper sulphate	photocatalytic activities	CuO NPs display higher catalytic activity compare to Ni@Fe3O4 NPs	[167]
19	Sida acuta	Leaf	Copper sulphate	Antibacterial	Higher antimicrobial activity against the growth of studied infectious pathogens.	[168]
20	Bauhinia tomentosa	Leaf	Copper sulphate	Antibacterial	CuO NPs offered antibacterial efficacy qualify for utilization in biomedical applications	[169]
21	Capparis spinosa	Leaf	Copper sulphate	Iron Sensing	The sensing potency of CuONPs towards Fe2+ and Fe3+ was higher than other tested metal ions	[170]
22	Fortunella japonica	Fruit	Copper sulphate	Sensing and remediation	The CuONPs sensor exhibited quality reproducibility and selectivity towards the analyte	[171]
23	Acalypha indica	Leaf	Copper sulphate	cytotoxicity activity	CuONPs exhibit good cytotoxicity activity against MCF-7 breast cancer cell lines	[172]
20	Zea mays	Husk	Copper acetate	Antibacterial	It showed effective inhibition against the growth of Pseudomonas aeruginosa and Bacillus licheniformis than Escherichia coli and Staphylococcus aureus	[173]
21	Eryngium campestre	Leaf	Copper sulphate	Remediation	promising nanoremediation potential for wastewaters containing heavy metals	[173]
22	Froriepia subpinnata	Leaf	Copper sulphate	Remediation	promising properties of nanoremediation of soil, and ground waters	[174]
22	Tabernaemontana divaricate	Leaf	Copper sulphate	Antibacterial	It showed maximum zone of inhibition against urinary tract pathogen at 50 Ng/ml	[175]

Probable mechanism for the toxicity of CuONPs against bacteria

The presence of CuO produces reactive oxygen species which interact with bacterial cell membrane to aid the penetration of CuONPs into the bacterial cell. The disturbances caused by CuONPs in the cell membrane of the bacterial causes some malfunctions in the bacterial cell which results into the inhibition of the growth of the bacterial species which might finally lead to their death [137]. The smaller size of CuONPs (nanometer) compare to the pore size of bacterial cells (micrometer) allows the easy penetration of CuONPs into the cell membrane without any interference [138]. The destruction of the bacterial membranes by CuONPs could be via production of reactive oxygen species and radicals or by direct cell damage since superoxide and hydroxyl radicals are produced by metal oxides (CuO) [139]. The abundance of carboxyl and amines groups on bacterial cell surface could possibly attract Cu2+ ions towards the cell [139, 140, 141]. Therefore, the probable antibacterial mechanism can be associated with gene toxicity, mechanical damage or oxidative injury. The probable antibacterial toxicity is showed in Figure 3.

Figure 3

Probable mechanism of CuONPs toxicity against bacteria.

Anticancer application

The anticancer investigation of CuONPs biosynthesized using the extract of black bean via the sulforhodamine-B assay revealed some alteration in the mitochondrial structure when incubated with CuONPs, the growth of cervical carcinoma cells were also greatly reduced when treated with CuONPs [142]. Report have shown that CuONPs mediated from Ficus religiosa had potential anticancer efficiency against the growth of A549 adenocarcinomic human alveolar basal epithelial cells [143]. The recommendation of CuONPs in development and design of delivery carriers for cancer cell targeting due to demonstrated prominent toxicity accentuated as oxidative stress damage and DNA damage in cancer A549 lung cells has been made [119]. The cytotoxicity of CuONPs mediated from the leaf extract of Pterolobium hexapetalum against human breast cancer cell line (MDA-MB-231) clearly showed enhanced effectiveness [118]. Stating the importance of toxicity analysis in selecting nontoxic nanoparticles with distinctive biological activities, report on the invitro toxicity investigation of phytosynthesized CuONPs reveals that they exhibit better toxicity efficacy that are beneficial in biomedical application when compared with chemically synthesized nanoparticles [145]. The report from the toxicity evaluation of CuONPs mediated from Olea europaea via animal model using 25 healthy male albino mice reveals that the CuONPs induces weight loss and exhibited dose-dependent toxicity [146]. Several studies have shown the cytotoxicity of CuONPs against cancer cell growth [147, 148, 149]. Literature reports on the anticancer potency of CuONPs are summarized in Table 4, while the probable mechanisms of CuONPs induced cytotoxicity in cancer cell lines is presented with Figure 4.

Figure 4

The probable mechanisms of CuONPs induced cytotoxicity in cancer cell lines.

The probable mechanisms of CuONPs induced n class="Disease">cytotoxicity in cancer cell lines.

Catalytic application

Metallic and metal oxide nanoparticles has been reported to exhibit good photocatalytic efficiency [150, 151, 152, 153]. The photocatalytic degradation assessment of green synthesized CuONPs on RB dye revealed 94% degradation efficiency to the fifth cycle, which demonstrates the durability of the phytosynthesized CuONPs rendering it a good photocatalytic agent [154]. Furthermore, the comparative catalytic study of CuONPs and zinc oxide nanoparticles (ZnONPs) for basic violet 3 degradation indicated that ZnONPs exhibited higher catalytic activity than CuONPs. The degradation of basic violet 3 proceeded with pseudo-first-order kinetics [120]. CuONPs synthesized using Thymus vulgaris leaf extract was reported as an outstandingly heterogeneous catalyst used in N-arylation of amines and indoles due to the remarkable percentage yield of N-arylated products obtained. The recovery and recycling of the catalyst for auxiliary catalytic reactions without ant loss in activity was also attained [155]. The photocatalytic analysis of CuONPs mediated from Aloe Vera leaves under solar simulator light irradiation indicated that CuONPs completely degraded methylene blue in 10 min. This high activity is traceable to the phyto-constituents in Aloe Vera leaves [156]. More findings on the catalytic efficiency of CuONPs has been reported [157]. The schematic representation of the degradation mechanism of CuONPs is showed in Figure 5.

Figure 5

A schematic representation of degradation of some pollutants using the CuONPs.

Conclusion

The method used in the synthesis of CuONPs predominantly affect the ecological identities as well as their physiochemical and morphological properties, which can influence their biological and catalytic applications. We discuss elaborately the biological method of synthesizing CuONPs from plant which offers great opportunity to medicinal institutes and other industries due to its biological activity and mode of synthesis. The principal application of CuONPs in biomedical and waste treatment is attributed to their antimicrobial efficiency which depend largely on the morphological properties. The recent characterization techniques used in examining the identities of CuONPs are well highlighted. The efficiency of biosynthesized CuONPs as anticancer, antioxidant, antibacterial and effluent treatment has been properly discussed. The mechanism of synthesis and toxicity are well explicated. To improve the biological applications of CuONPs more research work should focus on possible route of minimizing CuO-NPs’ toxicity while maintaining and improving their biological efficiency.

Declarations

Author contribution statement

All authors listed have significantly contributed to the development and the writing of this article.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Competing interest statement

The authors declare no conflict of interest.

Additional information

No additional information is available for this paper.