Antibacterial,antifungal,antiviral,and photocatalytic activities of TiO 2 nanoparticles,nanocomposites,and bio-nanocomposites: Recent advances and challenges

Introduction

Biological contamination of medical devices and implants is a growing issue that causes medical complications and augmented costs. ¹ In the fight against biological contamination, the creation of artificial surfaces, which reduce microbial adhesion and produce lethal activity or combined effects, has emerged as a major global strategy. ² Advances in nanotechnology and biological sciences have made it possible to design intelligent surfaces to reduce infections. However, the clinical performance of these levels depends greatly on the choice of substance. ³ In this regard, focusing on antimicrobial surfaces coated with applied materials such as cationic polymers, metal coatings and anti-fouling micro/nanostructures are critical issues. ⁴ In recent years, the treatment of infectious diseases is facing a crisis because treatment options against bacterial pathogens or new viral pathogens are limited by common antibiotic resistance. ⁵

The emergence of microbial resistance in various sectors such as food, textiles, medicine, water disinfection and food packaging leads to an ongoing process in search of new antimicrobials. ⁶ Increasing resistance of some bacteria to some antibiotics and toxicity of some organic antimicrobials in the human body has increased the interest in producing inorganic antimicrobials. ⁷ Among these compounds, metal compounds and metal oxides have attracted considerable attention due to their broad-spectrum antibacterial activities. Antimicrobial nanoparticles (NPs) have shown excellent and different activities as one of the major properties of nanomaterials.^8–10

Nano is a prefix that is used to define one billionth (10⁻⁹) parts of materials, and therefore it can be said that nanotechnology is manipulation of materials in the size range of 1–100 nm.^11,12 The field of medical nanotechnology as a whole includes the properties, composition, and medical application of nanomaterials and is actually an essential field for the study and design of drugs as well as molecular engineering in a small scale as an efficient way. ¹³ Humans have obtained the benefits of nanotechnology for so long, without the proper skills to take advantages of this technology, of which the Roman Lycurgus cup is a prime example. ¹⁴ It was not until 1959, however, that nanotechnology came to the attention of physicist Richard Phillips Feynman, in which he discovered the concept of manipulating matter at the atomic level. Fifteen years later, in 1974, it was termed “nanotechnology” by Norio Taniguchi from Tokyo University, and the term was used to describe processes in the nanometer size range. ¹⁵ Although nanotechnology became a familiar term in research until the discovery of fullerenes in the 1980s, it is also the beginning of the golden age of nanotechnology. Today, nanotechnology has potential applications in a variety of fields such as information technology, drug delivery, pollution control, and the production of several unique materials. ¹⁶ There are various organic and inorganic nanomaterials such as metal and metal oxide NPs. Among the metal/metal oxide NPs, TiO₂NPs have obtained a special attention owing to both catalytic and antimicrobial capacities.^17,18 Therefore, here, we tried to present recent advances and challenges about synthesis methods, antimicrobial, and photocatalytic activities of TiO₂NPs to achieve a deep viewpoint for future studies.

Synthesis of metal/metal oxide NPs

Production of metal-based NPs as a technology can be made in two main approaches of top-down and bottom-up (Figure 1). However, the usability of these methods has only been described in recent decades, metal-based NPs being widely exploited in many medical, cosmetics, electro-optical, catalytic, and textiles productions. ¹⁹ In recent years, metal-based NPs are silver, gold, copper, iron, and zinc have been used in various industrial and medical sections. In this regard, transition metals appear to be the best candidates for the synthesis of metal-based NPs because their d sub-shell is partially filled, activating redox (reduction to zero-valence atoms). ²⁰

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Figure 1.

The main methods for the synthesis of nanomaterials. ²¹

The various physical and chemical synthesis methods can be utilized to prepare metal/metal oxide NPs. In physical methods, top-down approach (Figure 1), bulk metals under the effect of mechanical are forced and turned into smaller pieces in a very simple way, which have relatively dispersed size. In bottom-up methods, chemical methods, by organic solvents or biological sources such as different types of plants and microorganisms, NPs have been obtained from metal atoms followed by the growth of NPs according to LaMer theory. ²² It is worth noting that, the size and morphology of NPs determine their activity, which can be controlled by synthesis reaction conditions. ²³ Studies about the crystal structure and morphology of TiO₂NPs have demonstrated that their synthesis is influenced by process parameters such as initial hydrothermal temperature, acid concentration and so on. ²⁴

The crystal structure and shape of the synthesized NPs of TiO₂ are both important properties that affect their physicochemical properties, so they are also effective in their antimicrobial properties Due to the crystal structures, the highest photocatalytic and antimicrobial activity is related to the anatase state. ²⁵ Some research suggests that the structure of anatase can destroy a bacterial membrane and cell wall by generating negative hydroxyl free radicals (^*OH) in a photocatalytic reaction. ²⁶ These properties are clearly explained in the below section.

Biosynthesis of TiO₂NPs

Living organisms involving pants, alga, fungi, bacteria, lichens, and viruses or their natural compounds can contribute to the production of NPs that are more stable than chemically synthesized NPs.^27–29 For instance, primary and secondary metabolites of medicinal plant species may synergize the therapeutic effects of NPs.^30,31 For microorganisms, Due to the repulsive forces created between the particles, which can be caused by the formation of electrical charges, NPs synthesized using microorganisms have less cumulative behavior. The application of NPs mainly depends on their size, shape as well as stability. Therefore, researchers are focusing more on the biogenic synthesis of NPs that can meet the criteria. TiO₂NPs, which are naturally present in the three crystalline variables anatase, rutile and brookite (Figure 2), can be produced using biological agents.^32,33

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Figure 2.

(a) Anatase, (b) rutile, and (c) brookite of TiO₂.

Extensive research has been conducted on the biosynthesis of NPs. Nano bio-particle Synthesis One of the growing topics is the field of nanotechnology. There are various reports on the use of bacteria, fungi, algae, plant materials, and enzymes for the biosynthesis of NPs.^34,35 Mechanisms involved in the microbial synthesis of NPs include; Biological adsorption, extracellular complexation or deposition of metals, bioaccumulation, flow systems in solution change, toxicity through reduction or oxidation and the absence of specific metal transport systems.^36,37 Plants with primary and secondary metabolites can participate in NPs formation, as an example, proanthocyanin polyphenols of grape seed extract with functional -OH groups played the main role in Ti⁴⁺ reduction followed by nucleation TiO₂NPs. ³⁸

Antimicrobial activity

Large surface-to-volume ratio, high aspect ratio, and reactivity have made NPs particularly TiO₂ NPs as efficient antimicrobial agents. As mentioned in the above sections, living organisms or their materials are used to synthesize metal/metal oxide NPs. For example, TiO₂NPs with the main size of 18.42 and antibacterial and antibiofilm effects on Pseudomonas aeruginosa and Staphylococcus saprophyticus strains were prepared by proanthocyanin polyphenols of grape seed extract. ³⁸ Carbon quantum dots (CQDs)-TiO₂ NPs with a particle size of 22.23 nm and antibacterial effects on E. coli and S. aureus were impregnated into bacterial cellulose (BC) to obtain the nanocomposite suitable for effective wound dressing. ³⁹ For antifungal activity, TiO₂NPs (the size range of 10–25 nm with spherical/rod shapes and crystal structures of 20% rutile and 80% anatase) showed similar minimum fungicidal concentrations (MFCs) of 256–512 ppm against Candida spp. compared to ZnONPs (the mean size of 20 nm in spherical morphology). ⁴⁰ In addition, the attachment of AgNPs to the cell wall of C. albicans was followed by damaging of the cell wall and the cytoplasmic membrane of fungi upon treatment at the concentrations of 500 and 250 ppm of myco-fabricated AgNPs (a spherical shape with a diameter range of 2–15 nm) by oropharyngeal Candida glabrata. As another example, C. glabrata showed minimum inhibition concentration of 0.125 ppm under spherical AgNPs (the diameter range 1–24 nm) biosynthesized by filtrated suspension of Aspergillus sydowii fungi. ⁴¹ In addition, a hydrothermal method was applied for decoration of TiO₂@ZnO nanocomposites (aggregated and spherical shape) with AuNPs having antifungal activity toward Candida albicans (MTCC 282) and antiproteinase activity (50% inhibition at 100 ppm) appropriate for treatment of human immunodeficiency virus (HIV) infection. ⁴² For the antiviral study, comparatively, half-maximal inhibitory concentration (IC₅₀) amount of 526 and 568.6 ng/mL were observed for ZnONPs and TiO₂NPs (the particle diameter of 470.6 nm and zeta potential of −5.92 mV), respectively against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ⁴³ Moreover, according to a molecular docking study, ZnONPs prepared by hesperidin, a flavanone disaccharide extracted from orange peel exhibited a significant antiviral activity against hepatitis A virus. ⁴⁴

Photocatalytic activity

The photocatalytic activity of TiO₂ with the large bandgap of 3.2 eV activated under UV light can produce reactive oxygen species (ROS) including species such as superoxide singlet oxygen (¹O₂), anion radical (O₂^*–), hydroxyl radical (^*OH), and perhydroxyl radical (HO₂^*). ⁴⁵ These ROS catalyze the reaction cascade inside the microbial cell, which leads to damage of biological macromolecules and their death. The formation of hydrogen peroxide (H₂O₂) also plays an important role in its antimicrobial activity. The chemical matrix has been functionalized by adding 10 wt % of TiO₂ NPs, which showed respectively 95% and 80% inhibition of E. coli and S. aureus due to the photocatalytic properties of TiO₂ under UV light exposure for the period of 1 h. ⁴⁶ Under visible light irradiation for 60 min, 96% of methylene blue was degraded by 4 mol % of Ag-doped TiO₂NPs. In addition, 8 mol % doping of AgNPs with TiO₂NPs showed significant antibacterial activity as inhibition zone of 26.4%, 27%, 30%, and 29% against E. coli, P. aeruginosa, Klebsiella pneumonia, and Enterobacter cloacae, respectively. ⁴⁷ Similarly, loading AgNPs (the size range 3–5 nm) on TiO₂ nanotubes (the length range 200–400 nm), Ag/TiO₂ nanocomposites at a concentration of 20 µg/mL revealed 99.99% growth inhibition of S. aureus after 1 h under sunlight irradiation. ⁴⁸ Modification of TiO₂NPs by polymeric materials specifically natural polymers is interesting because of the biocompatibility of these materials. For instance, chitosan with a positive charge was applied to prepare poly(vinyl alcohol)/TiO₂/chitosan/chlorophyll bionanocomposites in a simple one-pot synthesis. These bionanocomposites showed the inhibition zone of 19.8 and 20.8 mm for E. coli and S. aureus, respectively under light-emitting diodes (LED) light irradiation. In this study, chlorophyll had a natural photocatalyst role, which was extracted from fresh spinach. ⁴⁹ Biosynthesized TiO₂NPs (hexagonal shape, polydispersity index (PDI) = 0.262 with the average size of 17.90 nm) via the aqueous extract of Acacia catechu at 5 μg showed no resistance effect in S. aureus and also degradation of carcinogenic chemicals dyes of 4 nitrophenol, Rhodamine B, and Rose Bengal. ¹⁸

Conclusions

In this review, recent advances and challenges about synthesis methods specifically biosynthesis of TiO₂NPs as well as antibacterial, antifungal, antiviral, and photocatalytic activities of these NPs or their nanocomposites and bionanocomposites were discussed. For chemical synthesis, reaction conditions such as temperature, pH, concentrations of precursors, and reaction time should be controlled to get TiO₂NPs with suitable morphology and size properties. In addition to physicochemical characteristics of NPs, type of microorganism, for instance, Gram-positive or Gram-negative bacteria and the photocatalytic ability of TiO₂NPs can change antimicrobial activity under UV irradiation. Surprisingly, doping TiO₂NPs with other metal or metal oxide NPs may increase antimicrobial activity even under visible light. Totally, there are a plethora of in vitro studies about antimicrobial and photocatalytic aspects of TiO₂NPs, nanocomposites, and bionanocomposites; however, more comprehensive in vivo studies confirm the efficiency of these NPs in physiochemical conditions are needed.