A Comprehensive Review of Synthesis, Properties and Applications of TiO₂ and ZnO Nanoparticles

1. Research Scholar, Department of Prosthodontics, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, India. 2. Professor, Department of Prosthodontics, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, India. 3. Professor, Department of Pharmacology, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, India. 4. Research Scholar, Department of Prosthodontics, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, India. 5. M Tech Student, Department of Mechanical Engineering, Indian Institute of Technology, Chennai, Tamil Nadu, India.

Abstract

Nanotechnology is an advancing field of science with the potential to improve the quality of life through its applications in the field of nanomedicine. It refers to the technology of precisely manipulating atoms and molecules and developing new materials with nanoscale dimensions. Nanoparticles (NPs) typically range in size from 1-100 nm. Nanoparticles play a major role in the prevention of infections, so they can be utilised as nanocarriers with antimicrobial therapeutic actions. This article is a literature review on different methods of synthesis, properties, and biomedical applications of Titanium Dioxide (TiO₂) and Zinc oxide (ZnO) nanoparticles. Since nanoparticles can be biomodified by cost-effective methods, the use and applications of NPs will increase in the future. The unique properties of nanoparticles make them useful in various fields of science such as materials, engineering, electronics, food science, and biomedicine. Due to their advantages, nanotechnology has gained the attention of researchers, especially for its promising applications in the healthcare system for better diagnosis and treatment.

Bioimaging, Green synthesis, Nanobiomedicine, Nanotechnology, Titanium dioxide, Zinc oxide

Nanomaterials have been defined as natural, man-made, or incidental materials that comprise particles as agglomerates or masses or in an unconstrained state where 50% or a higher number of the particles display one or more outer dimensions within the range of 1-100 nm (1). A nanoparticle is the most essential component in the manufacture of a nanostructure (2). According to the British Standards Institution, a nanoparticle exhibits and confines its diameter and all its fields in the nanoscale (3). The term ‘nano’ refers to the Greek prefix meaning very small or dwarf. Nanoscience is a conjunction of materials science, physics, and biology, which includes the synthesis of materials at atomic and molecular scales, whereas nanotechnology deals with the capacity to observe, quantify, assemble, control, and synthesise matter confined to the nanometer scale (4). They are also denoted as “zero-dimensional” nanomaterials (5). Nanotechnology is defined as the application of scientific knowledge to manipulate and control matter at the nanoscale (6). The International System of Units (SI) uses the term nanoparticle to designate a reduction factor of 109 times. It covers structures whose size is above molecular dimensions and below macroscopic ones (generally >1 nm and <100 nm) (7). The American physicist Richard Feynman, considered the father of nanotechnology, introduced the concept in 1959 during an annual meeting of the American Physical Society at the California Institute of Technology in his lecture titled “There’s Plenty of Room at the Bottom.” He explained the method of synthesis by the manipulation of atoms, which became a roadmap for new development (4). The term nanotechnology was first defined by Norio Taniguchi of the Tokyo Science University at the international conference on industrial production in 1974 to describe the processing of materials with nanometer accuracy and the creation of nanosized particles (4). The present review describes the different methods of synthesis, properties, and biomedical applications of TiO₂ and ZnO nanoparticles.

Discussion

Nanoparticles can be classified based on the following criteria (8):

1) Origin: Natural and anthropogenic.

2) Size: Ranging from 1-10 nm, between 10-100 nm.

3) Chemical composition: Organic substances, inorganic materials, and elements of the living kingdom.

4) Dimensions of existence (7):

a) One-dimensional nanoparticles: The system includes thin films ranging from 1-100 nm or monolayers, which find their application in information storage systems, the production of fiber-optic systems, chemical and biological sensors, magneto-optic and optical devices.

b) Two-dimensional nanoparticles: Carbon Nanotubes (CNTs) are carbon atoms existing in hexagonal networks, appearing as a layer of graphite rolled up into a cylinder ranging about 1 nm in diameter and 100 nm in length. They can be single-walled or multi-walled.

c) Three-dimensional nanoparticles:
i) Fullerenes (Carbon 60): Spherical cage-like structures with a large number of carbon atoms, containing C60. They exist like a hollow soccer ball made up of interconnected carbon hexagons and pentagons.
ii) Dendrimers: A novel category of controlled-structure polymers presenting dimensions ranging from 10 to 100 nm in diameter along with numerous functional groups on their surface.
iii) Quantum Dots (QDs): These are tiny devices that contain a single droplet of free electrons made up of colloidal semiconductor nanocrystals of 2 to 10 nm in diameter. Widely used QDs include Cadmium Telluride (CdTe), Cadmium Selenide (CdSe), Indium Phosphide (InP), and Indium Arsenide (InAs).

5) Based on carbon composition (9):

a) Organic nanoparticles: Include dendrimers, micelles, liposomes, and ferritin. They are non toxic, biodegradable, and exhibit sensitivity to electromagnetic and thermal radiation.

b) Inorganic nanoparticles: Particles that are not composed of carbon atoms constitute inorganic nanoparticles. They include metal and metal oxide-based nanoparticles.

i) Metal-based.
ii) For the synthesis of nanoparticles, commonly used metals are Cobalt (Co), Aluminium (Al), Cadmium (Cd), Zinc (Zn), etc.
iii) Metal oxides based.

Commonly synthesised metal oxides include Cerium Oxide (CeO₂), Aluminium Oxide (Al₂O₃), Iron Oxide (Fe₂O₃), Silicon Dioxide (SiO₂), Magnetite (Fe₃O₄), Titanium Oxide (TiO₂), Zinc Oxide (ZnO), etc.

c) Carbon-based: Nanoparticles made entirely of carbon atoms are referred to as carbon-based. They can be further categorised into graphene, Carbon Nanotubes (CNT), fullerenes, carbon nanofibres, carbon black, and occasionally activated carbon in nano size (9).

The major factors influencing nanoparticle synthesis include pressure, temperature, time, size and shape of the particle, pore size, and expenditure of preparation (10).

Approaches in the Production of Nanoparticles

There are various approaches for the production of nanoparticles:

1) Top-down approach: This approach comprises the breaking down of bulky larger particles into particles of the nano range by the process of attrition process, milling, and electro-explosion wire techniques. Although the process is less time-consuming, it entails more energy consumption and is used in laboratory experimentation [9,10]. Methods employed in the top-down approach include physical and chemical vapour deposition, electron beam lithography, ion implantation, as well as X-ray lithography [10,11].

2) Bottom-up approach: This includes the diminishment of constituent materials to the very atomic level with multiple supplementary procedures leading to the growth of nanostructures. The physical forces acting on the nanostructure are utilised to pool the particles into a larger one during the assembling procedures (9). The methodology focuses on the concept of molecular recognition or self-assembly, which refers to self-budding on more things of one’s own kind from themselves. Scientists prefer the bottom-up approach because of its benefit of accurate control of particle size causing decent optical, electronic, and other related properties (11).

Multiple methods employed in the bottom-up approach include hydrothermal synthesis, colloidal precipitation, sol-gel synthesis, organometallic, chemical route, and electrodeposition (10),(11).

Methods of synthesis of nanoparticles:

A. P Physical methods (10):

1. Mechanical method: In the mechanical ball milling method, various forms of mills used include planetary, rod, vibratory, and tumbler. The container comprises steel or carbide hard balls. Nanocrystalline Co, Ag-F, etc., are manufactured by means of this method. The balls-to-material ratio is generally kept at 2:1. Inert gas or air is used to fill the container, and it is rotated at a very high speed around the central axis. The materials are hard-pressed between the walls of the balls and the container. In the procedure known as the melt-mixing process, molten metal streams are mixed at high velocity with turbulence to form nanoparticles.

2. Pulse laser ablation: Inside a vacuum chamber, the target sample is placed onto which the high-pulsed beam of laser is focused, and plasma is generated, which is formerly transmuted into a colloidal solution of nanoparticles.

3. Pulsed wire discharge method: The most widely used method for the synthesis of metal nanoparticles. Pulsated current is utilised to vaporise a metal wire to yield vapour, which is later cooled by the presence of ambient gas to process nanoparticles.

4. Chemical vapour deposition: Upon the substrate surface, a thin film of gaseous reactant is deposited at around 300-1200°C. Here a chemical reaction happens between gas and the heated substrate and combining gas, producing a thin film of the product on the substrate surface. The pressure of application ranges from 100-105 Pa.

5. Laser pyrolysis: Synthesis of nanoparticles using a laser beam is known as laser pyrolysis. An intense laser beam is used to disintegrate the mixture of gases.

6. Ionised cluster beam deposition: The arrangement comprises a source of evaporation, a beam of electrons to ionise the clusters, a nozzle providing expansion facility for the material, an arrangement to accelerate the clusters, and a substrate for nanoparticle deposition, all components stored in a suitable vacuum chamber. Through the action of an electronic beam, ionised collections are obtained.


B) Chemical methods (10),(11):

1. Sol-gel Method: This method includes various steps of condensation, hydrolysis, and thermal decomposition of metal alkoxides. The newly formed stable solution is termed as a sol. Through the process of hydrolysis or condensation, the gel is produced with remarkable viscosity.

2. Sonochemical synthesis: Pd-CuO nanohybrids have been effectively synthesised by sonochemical fusion with copper salt in the presence of palladium and water. The commercially used source is either palladium salts or pure metallic palladium (Pd).

3. Co-precipitation method: The method involves rapid diffusion of polymer-solvent into a non solvent polymer phase by mixing the polymer solution at the end. The interfacial tension at these two phases can yield nanoparticles.

4. Inert gas condensation method: Metals are placed inside a chamber filled with neon, argon, or helium, and the metal is vaporised. The gases start to cool in the presence of liquid nitrogen and form nanoparticles of 2-100 nm.

5. Hydrothermal Synthesis: One of the most commonly used methods in which a chemical reaction is initiated at temperatures ranging from room temperature to extreme levels for the synthesis of nanoparticles.

C) Biological methods (10),(11):

1. Synthesis using microorganisms: It involves either extracellular biosynthesis or intracellular biosynthesis making use of microbes capable of separating metal ions. Pseudomonas stutzeri Ag 295 is often found in silver mines, capable of collecting silver inside or outside the cell walls.

2. Synthesis using plant extracts: For the manufacture of gold nanoparticles, leaves of the geranium herb (Pelargonium graveolens) have been used. 1 mL 1 mmol aqueous solution of silver nitrate is combined with 5 mL of the plant extract for the same.

3. Synthesis using algae: Algae extract is prepared in an aqueous solvent or an organic solvent by heating or boiling it for a defined period. Algae solution and molar solutions of ionic metallic complexes are commonly incubated, either with continuous stirring or without stirring, for a defined duration under controlled conditions.

Physicochemical properties of nanoparticles:

a) Mechanical properties: Nanoparticles of non metallic materials are fragile and do not possess remarkable mechanical properties like plasticity, toughness, ductility, or elastic properties, whereas organic nanomaterials are flexible materials. The superior properties of nanoparticles are attributed to the diverse interaction forces between the nanoparticles and the contacting surface. The significant ones are electrostatic force, capillary forces, hydration forces, and van der Waals forces comprising Keesom force, Debye force, and London force (12).

b) Thermal properties: When the size of the nanoparticles decreases, the surface area to volume ratio increases hyperbolically. This higher surface-to-volume ratio allows a greater number of electrons for the transfer of heat compared to larger sizes. The superior thermal properties also result from micro convection, which occurs as a result of the Brownian motion of particles (12).

c) Magnetic properties: One of the notable size-dependent phenomena exhibited by nanoparticles is superparamagnetism, which is displayed in the presence of a magnetic field.

d) Electronic and optical properties: Metallic and semiconductor nanoparticles display certain characteristic properties like photoluminescence emission, linear absorption, and nonlinear optical properties related to the Localised Surface Plasmon Resonance (LSPR) effect and quantum confinement. Improved crystallinity and small size of biogenic nanoparticles render them superior features compared to chemical nanoparticles (12).

e) Catalytic properties: The application of nanoparticles, called nano-catalysis, is gaining more interest these days. When compared to bulk materials, nanoparticle catalysts show enhanced properties such as reactivity and selectivity (12).

Synthesis of titanium oxide nanoparticles: There are two methods of synthesising TiO₂ NPs.

1) Sol-gel method (13),(14)

There are two methods of sol-gel preparation:

a) Alcohol-based method: Ti (OC₂H₅), Ti(OC₂H₇)₄, and Ti(OC₄H₉)₄ are the major metal oxide precursors of titanium oxide nanoparticles. The metal-oxide bond in these alkoxides becomes highly polar and reactive because of the high electronegativity difference between titanium and oxygen. Addition of water leads to simultaneous hydrolysis and condensation reactions producing a gel (13).

b) Aqueous-based process: Precipitation and peptisation are the two major steps in the aqueous-based sol-gel process in the production of these nanoparticles. When a base is added, the inorganic metal salt rapidly hydrolyses to a gelatinous precipitate. The excess electrolyte is then washed-off. The process of the direct breakdown of a substance into colloidal particle size by the addition of a peptising agent is called peptisation (13).

2) Hydrothermal method: One of the suitable synthetic approaches to titanium nanoparticle manufacture is the hydrothermal method because of its several advantages like low production cost, controllability of reaction conditions, appropriate crystallisation temperature, being environmentally friendly, and low energy consumption.

Pure TiO₂ powder (Degussa P25, 98%) sized 25 nm, along with a crystalline structure of mixed anatase and Rutile (80:20), is used in this method. About 0.5g of titanium oxide powder is added to a 10M 40 mL NaOH aqueous solution, then stirred vigorously for half an hour. Later, this mixture can be transferred for hydrothermal treatment to a stainless steel autoclave lined with Teflon and kept at 200°C for 48 hours in a muffle furnace. Following the reaction, the white precipitate needs to be separated from the autoclave and cooled at room temperature, subsequently washed with 0.1 M HCl acid solution and deionised water. This process of acid wash should be continued until almost all the Na+ ions are removed. After removing sodium ions, the resultant white precipitate, after the centrifugation process, should be dried in an oven at 60°C and then calcined at 250°C for two hours (15).

Properties of TiO₂ nanoparticles: TiO₂ nanoparticles are well known for their chemically inactive nature, non toxicity, low cost, high refractive index, excellent antibacterial effects, corrosion resistance, and impressive microhardness (16). They have impressive wear resistance, lightness, high strength, mechanical resistance, and electrical conductivity, low thermal diffusivity, and conductivity. They are white in colour and ductile in their pure form, so they can be readily customised to the required form and type (1). Considering the non toxicity, the American Food and Drug Administration (FDA) has approved the incorporation of TiO₂ for use in drugs, human food, cosmetics, and food contact materials (1). (Table/Fig 1) lists the medical applications of TiO₂ nanoparticles (17),(18),(19). (Table/Fig 2) summarises the dental applications of TiO₂ nanoparticles (16),(17),(20),(21),(22),(23),(24),(25). Disadvantages are reported with titanium nanoparticles, like reduced interaction with surrounding tissue and bioactivity, which can be overcome by surface coating of this metal with biocompatible compounds (17),(25).

Synthesis of zinc oxide nanoparticles: The synthesis of zinc oxide nanoparticles can be categorised into conventional (physical, chemical, and biological methods) and non conventional (reactor-based) methods (26).

The synthesis of zinc oxide nanoparticles can be categorised as follows:

1. Conventional

a. Physical methods: Physical methods comprise arc plasma, thermal evaporation, physical vapour deposition, ultrasonic irradiation, and laser ablation.

• Arc plasma method: The most common method to synthesise nanoparticles is an electric arc discharge method using Zinc rod, dry air, and a carbon rod as the cathode.
• Thermal evaporation: Zinc oxide powder is mixed with graphite, a reducing agent, at a temperature of 1000-1100°C to produce ZnO nanostructures.
• Physical vapour deposition: ZnO nanowires are fabricated at a low temperature of 450°C, with an increase in diameter as the temperature rises.
• Ultrasonic evaporation: It is a natural method of fabricating nanoparticles in a solution phase operation without changing the character of the particles.
• Laser ablation: An effective method for fabricating nanoparticles using all types of materials by adjusting parameters of the laser such as duration, wavelength, temperature, etc.

b. Chemical methods: Chemical methods employ the precipitation method, hydrothermal method, and chemical vapour deposition technique (26),(27),(28).

• Precipitation method: A precursor solution of Zinc salt, like Zinc nitrate, is treated with a reagent, such as acid or base, under high temperature and pressure to form nanoparticles.
• Hydrothermal method: An aqueous solution of precursor chemicals is treated at high temperature and pressure to form nanoparticles.
• Chemical vapour deposition method: A transport agent, like graphite, is added to zinc and heated at high temperature, then cooled to form nanoparticles.

The solid-phase synthesis techniques involve mechano-chemical and mechanical ball milling methods. The liquid-phase techniques comprise laser ablation, exploding wire, solution reduction, and decomposition processes.

Gas phase processes include gas evaporation and spark discharge processes (29).

c. Biological methods: Biological methods are predominantly an eco-friendly approach, which utilise biochemical and biotechnology methods and extraction from plants, as well as animals (26),(27),(29).

Green synthesis of ZnO NPs is a simple extraction technique employed after cleaning appropriate plant parts like leaves, stem, fruits, flowers, roots, peels, etc., with water. Commonly involved plants are P hysterophorus, Solanum nigrum, Purnus domestica, etc., which are subjected to elution, filtration, and separation.

The resultant extract is either dried or used to react with a zinc precursor under diverse conditions of pH and temperature. The phytochemicals used include numerous bio-active compounds like polyphenols, saponins, and flavonoids, which chelate with the metal ion and also stabilise the NPs. The underlying mechanism in the production of ZnO NPs is the simultaneous reduction and oxidation of cationic zinc ion by the phytochemicals present in the extracts. Upon completing the reaction, the product is exposed to an annealing process to obtain ZnO NPs. The ZnO NPs produced by means of plant extract show higher photocatalytic, antimicrobial, and antioxidant properties compared to the NPs synthesised by fungi, bacteria, algae, and yeast (27),(30).

The common sources of microbes used in the production of zinc oxide nanoparticles are Aeromonas hydrophila, Aspergillus aeneus, Pichia kudriavzevi, etc. The procedure involves selecting microbes and providing optimal conditions for cell growth. ZnO NPs are thoroughly washed with distilled water and ethanol, subsequently dried at 60°C overnight to obtain a white powder of ZnO NPs (29),(31).

2. Non conventional (reactor-based) methods: Microfluidic reactor-based method: It is a simple method to synthesise materials on the benchtop. Compared to the conventional method, this method utilises fewer chemicals and causes less damage to the environment and health (26),(27).

Properties of ZnO NPs: The method of preparation and the morphology determine the physical and chemical properties of zinc oxide nanoparticles (32). Zinc oxide nanoparticles appear as a water-insoluble white powder (30). The distinctive physical and chemical properties include a high electrochemical coupling coefficient, remarkable chemical stability, paramagnetic characteristics, extensive radiation absorption capability, and exceptional photostability.

The absence of a center of symmetry in wurtzite, along with high electromechanical coupling, results in strong pyroelectric and piezoelectric properties, making it applicable for piezoelectric sensors and mechanical actuators (27),(29). The energy band of 3.37 eV and bonding energy of 60 meV render it remarkable chemical, electrical, and thermal stability. Because of its acceptable optical, electrical, and photocatalytic properties, zinc oxide nanoparticles are applied in solar cells, photocatalysis, and chemical sensors. The low toxicity and high UV absorption enable its use in the biomedical field (32).

Summary of the medical applications of ZnO nanoparticles has been given in (Table/Fig 3) (28),(32),(33),(34),(35). The dental applications of ZnO nanoparticles has been summarised in (Table/Fig 4) (35),(36),(37),(38).

Research in the field of nanotechnology enables us to synthesise new materials by direct control of matter at the nanoscale. Good control over the synthetic parameters will definitely help in manipulating the physicochemical properties of ZnO and TiO₂ NPs, thus utilising them in various branches of science such as material science, engineering, biology, biomedicine, and dentistry.

Conclusion

The TiO₂ and ZnO NPs exhibit most of the properties displayed by an ideal oral biomaterial; hence, they are employed as antimicrobial agents, prosthetic material, and in various biomedical fields. Nanoparticles play a vital role in modern medicine, from diagnosis to treatment planning. Biomedical applications of these nanoparticles have gained more interest among researchers and motivated them to do more research in this emerging frontier.

DOI and Others

DOI: 10.7860/JCDR/2024/69854.19399

Date of Submission: Jan 30, 2024
Date of Peer Review: Feb 20, 2024
Date of Acceptance: Apr 10, 2024
Date of Publishing: May 01, 2024

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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