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Abstract

Nanotechnology is a promising science with new aspects to fight and prevent various diseases using nanomaterials. The capability to expose the structure and functions of biosystems at the nanoscale level supports research leading to development in biology, biotechnology, medicine, and healthcare. This is predominantly advantageous in treating microbial infections as an alternative to antibiotics. However, widespread production, use, and misuse of antibiotics have input to the next-generation alarm for the emergence of multiple-drug-resistant pathogenic bacteria. Due to infectious diseases from these drug-resistant pathogenic strains, human mortality rates have consistently increased and are becoming an epidemic in our society. Consequently, there is a strong demand for developing novel strategies and new materials that can cope with these problems. The emergence of nanotechnology has created many new antimicrobial options. The small size of these nanomaterials is suitable for carrying out biological operations. Several metals and metal oxides, such as silver, copper, gold, zinc oxide, and iron oxide nanoparticle types have shown toxicity toward several pathogenic microbes. Metal-based nanoparticles have been broadly examined for a set of biomedical applications. According to the World Health Organization, the reduced size and selectivity of metal-based nanoparticles for bacteria have established them to be effective against pathogens causing concern. Metal-based nanoparticles are known to have nonspecific bacterial toxicity mechanisms, which not only make the development of resistance by bacteria difficult, but also widen the spectrum of antibacterial activity. Metal-based nanoparticle efficiency studies achieved so far have revealed promising results against both Gram-positive and Gram-negative bacteria. Here we discuss the potential nanomaterials to either treat microbial resistance or induce development of resistance. However, fundamental research is required to focus on the molecular mechanism causing the antimicrobial activity of nanomaterials.

Keywords

diseases antibiotics antimicrobial activity multiple drug resistance metals metal oxides

Introduction

The US National Science and Technology Council defined nanotechnology as the capability to work atom by atom at the molecular level, to synthesize new large structures that constitute new molecular organizations.¹ Basically, nanotechnology aims to exploit the characteristics of these devices and structures to gain knowledge about manufacturing and using them at supramolecular, molecular, and atomic levels.² Nanotechnology is also described as the integration and combinatorial study of medical engineering and scientific-technological advances at the nanometer level.³ Therefore, from the above-mentioned definitions, nanomaterial helps in enhancing the biological, physical, and chemical properties of any material.⁴ Similarly, biosystems engineering uses techniques and knowledge of biology to manipulate cellular, genetic, and molecular processes to develop services and products to make use of them in different fields from agriculture to medicine.⁵ It refers to the usage of engineering tools and biological principles to manufacture economically viable devices or products.⁶ This field either modifies the biological systems or mimics product development.⁷

The nanobiotechnology field is the fusion of both nanotechnology and biotechnology through which microtechnology is merged with a molecular biological approach.⁸ With this technology, molecular and atomic grade devices can be designed to either incorporate or mimic the biological systems to build tiny tools to either modulate or study it on a molecular basis.⁹ Therefore, nanobiotechnology can ease the avenues of life sciences by incorporating the applications of nanotechnology and information technology into biological systems.¹⁰

The small size of nanoparticles (NPs) is very appropriate for the delivery of the antimicrobial biological process. NPs of metals such as silver, zinc, copper, and iron have shown remarkable potential as bactericidal and fungicidal agents, representing their potential as competent antibiotic reagents in wound care and associated medical issues.⁵ These nanomaterials exhibited antimicrobial activity against several pathogenic viral and bacterial species. Nanomaterials nowadays show a potential platform for alternative measures to control bacterial infections as they offer long-lasting antimicrobial activity with insignificant toxicity, evaluated against small molecular antimicrobial agents that display short-term activity and environmental toxicity. The antimicrobial NPs physically destroy cell membranes of the organism which prevents the development of drug-resistance microbes.⁶

This review explores the basics of nanotechnology, including their potential impacts, challenges, and future prospects for biosystems engineering.

For over a decade, nanotechnology has undergone immense exponential growth in various medicinal and technological fields, and, because of their unique characteristics, nanomaterials have been widely applied as nanomedicine, and in electronics and energy.¹¹ Nanotechnology is a phenomenon involving variations of materials at macromolecular, molecular, and atomic levels; wherein it also involves the design, production, characterization, and application of systems and products on a nanometer scale.¹² Both nanoscience and nanotechnology are growing fields that have transformed various industries such as cosmetics, biotechnology, food sciences, electronics, and pharmaceuticals (as shown in Figure 1).¹³ Especially, the usage of nanotechnology in pharmaceutical research has led to the development of nanomedicines that operate in the nanometer scale range that provides a wide range of medical benefits in treating various infections and diseases.¹⁴ The nanomaterials used to carry out such applications are well defined with sizes ranging from 1 to 100 nm and are usually nanospheres. Nanotechnology develops nanomedicines by employing curative agents at the nanoscale level and making them able to move freely inside the human body when compared to large-sized materials.¹⁵

Figure 1.

Various fields involved in manufacturing engineered nanoparticles.

Nanomedicines have compatibility with biomolecules and thus help in molecular diagnostics, treatment, and prevention of various human diseases.¹⁶ Currently, NPs have shown a great impact on the development of scientific designs.¹⁷ The major disadvantage of living organisms for using NPs is their cytotoxic effects, which limit their usage in the clinical setting.¹⁸ There are several advantages in biomedical applications, such as entering the human body by inhaling the NPs and potentially accessing the organs through digestive and skin routes, which make the use of NPs an ideal approach.¹⁹ However, several factors play a key role while constructing a bio–nanointerface: (i) How the NPs interact with the biomolecules and other nanomaterials in the ecosystem.²⁰ (ii) The suitable design of NPs achieved through physicochemical properties to obtain a particular shape, surface charge, size, and dispersity.²¹ (iii) The biocompounds (cells, biomolecules, and proximal fluids) interacting with the NPs favor mechanical, chemical, and physical changes.²²

Nanoparticles

Nanomaterial refers to the manufactured, natural or incidental material which comprises particles either in aggregate or in the unbound state.²³ Structures such as carbon nanotubes (CNTs), graphene flakes, and fullerenes have their dimensions below 1 nm and are considered to be nanomaterial; also, the materials with a surface area to volume ratio are included in this category.²⁴ These nanomaterials are very promising in the medicinal field as they act as drug carriers. According to the European Union, size, shape, surface, chemical composition, surface charge, and protein corona are the physicochemical factors that help us in identifying an NP.²⁵

NP Size

In the field of nanotechnology, size plays a major role in various mechanisms involved in biological systems such as particle processing and cellular uptake.²⁶ Also, their smaller size, faster ion release rate, and interactions have a greater effect on this system.²⁷ The surface/volume ratio depends on the NP size; it increases with a decrease in the size of NP. This in turn increases their contact surface and toxic effects, thus making their penetration easier into the body.²⁸ A NP with <50 nm size exerts stronger toxic effects and connects to all the body tissues if it is given through intravenous injection.²⁹

The size of NPs is so important that it monitors pharmaceutical behavior and has a direct impact on various physiological activities.³⁰ If the size of the NP is >1 μm it might not enter the cell, but it interacts effectively with the absorbed proteins inside the cell. Also, an NP size >6 nm is difficult to accumulate in specific organs and cannot be excreted through the kidneys.³¹

Sonavane et al³⁰ studied the bioaccumulation and biodistribution of different sizes of gold NPs and reported that the smaller NPs accumulated very well in all the organs and stayed in the bloodstream for a longer period. Physicochemical characteristics of NPs and nanomaterials together with size, shape, chemical composition, physiochemical stability, crystal structure, surface area, surface energy, and surface roughness usually control the toxic appearances of these nanomaterials. This induces researchers to assess the role of these properties in decisive connected toxicity concerns. In this review, the problems are discussed pertaining to the physicochemical properties of nanomaterials related to the toxicity of the nanomaterials.³²

NP Shape

In nanotechnology, the shape parameter plays a very important physiochemical role that directly influences the toxicity of NPs.³³ NPs are of various structures and shapes viz. planes, fibers, tubes, and spheres. Depending on the shapes of NPs, they might influence certain mechanisms such as internalization, elimination, endocytosis, and biodistribution. For example, spherical NPs are relatively less toxic and are reported to have internalized faster and easier by endocytosis compared to rod-shaped NPs.³³

NP Surface Modification

NP and cell solubility, including its interactions, are completely dependent on the nature of the NP surface.³⁴ Surface coating of NPs can modify or alter the optical, electrical, magnetic, and chemical properties affecting their cytotoxic effects, influencing their toxicity, distribution, pharmacokinetics, and accumulation.³⁵ The surface chemistry affects colloidal behavior,³⁶ absorption, crossing the blood–brain barrier,³⁷ and binding of plasma protein to NPs.³⁸ When the surface charge of NPs increases even cytotoxicity increases³⁹ suggesting that the greater the positive charge the higher the endocytic uptake and cell electrostatic interactions.⁴⁰ Surface modification technique is one of the most important strategies applied in various biomedical fields to modulate and control the cellular internalization, increase stability, and decrease toxicity.⁴¹

NP Chemical Composition

NP chemistry is one of the important key factors that contribute to cell interactions. Researchers observed the chemistry of silver (Ag) and copper (Cu) NPs and studied their toxic effects in algae, daphnids, and zebra fish; there were no toxicity problems.⁴² The higher the concentration of NPs the greater is the aggregation and the toxicity is lower⁴³ because the larger particles are effectively removed by macrophages thus allowing the smaller particles to evade the defense mechanism.⁴⁴

Protein Corona

When NPs enter the body's bloodstream they interact with the biomolecules (proteins, carbohydrates, and DNA/RNA) and form a corona around them (shown in Figure 2).⁴⁵ This corona is usually composed of several proteins viz. apolipoproteins, immunoglobulin G, fibrinogen, serum albumin, and clustering that exhibit different affinity interactions.⁴⁶ Therefore, the biological identity and physicochemical properties of NPs change as soon as the protein corona is formed around it. Understanding the NP–protein interactions has become the main challenge in the field of nanomedicine due to their possible adverse effects such as thermodynamic, physicochemical, dynamic, and kinetic interactions.⁴⁷ NPs interact with various biomolecules depending upon the type of administration.⁴⁸ Biological environmental conditions such as temperature, physiological state, media components, and pH have become key factors in the process of protein corona formation.⁴⁹ Several proteomic analytical techniques, namely sodium dodecyl sulfate-polyacrylamide gel electrophoresis, isothermal calorimetric titration, liquid chromatography with tandem mass spectrometric quantification, centrifugation, and ultraviolet and visible spectrophotometry are used to determine or evaluate the NP–protein interactions.⁵⁰ Henceforth, a complete understanding of NPs relationships in the biological environment is essential to know their viability and stability.⁵¹

Figure 2.

Pictorial representation of protein corona formation: (i) the designed nanoparticle (NP), (ii) introduction of NP into the protein-rich medium/fluid, and (iii) the proteins are coated onto the NP.

Biosystem Engineering

Biosystems engineering is a newly developed scientific field used to develop new engineering solutions for forestry, medicine, energy, agriculture, environment, aquaculture, industry, and food. This field encompasses several other areas of engineering such as biotechnology (genetics, microbiology, and biochemistry engineering), physical sciences (physics, nanotechnology, chemistry, and materials science), electronics, chemical, biomedical, electrical, and mechanical engineering. Biosystems engineering is a special field that integrates life sciences with physical sciences and engineering to develop new products and techniques to meet global demands.

Applications of Nanotechnology in Biosystem Engineering

NPs are designed as such to achieve improved response in the Biosystems engineering field. Nanostructures have been widely applied with great interest in various medicinal fields. Nanobiotechnology is thus regarded as one of the most powerful aspects that help in developing new diagnoses, biosensors, bioimaging, and drug delivery techniques.⁵² Some of the important applications of NPs in biosystems engineering are listed in Table 1.

Table 1.

Applications of NPs in Various Fields.

Applied field	Type of NPs used	Remarks	References
Tissue engineering	TiO₂ and Au NPs in conjugation with polymer PLGA is used to increase the rates of cell proliferation.	Nanotechnology is combined with tissue engineering to replace or repair cells and to regenerate organs and CNS cells.	^53–55
Antimicrobial therapeutics	TiO₂ and Ag NPs exhibit antimicrobial properties which are coated onto the masks to eliminate virus and bacteria.	NPs coated onto the drugs have been reported to repel the microbes; it is due to the presence of a high surface/volume ratio.	^56–58
Gene therapy	Silica nanospheres along with NH₃ cation groups can deliver polymers, certain inorganic particles, cell lipids, and graphene.	Usually, NPs are potent in carrying the gene products and thus, are widely used in genetic material delivery into the living cells.	^59–61
Cell splitting	MNPs are mostly responsible for the separation of targeted biomolecules using a magnetic force.	Biomolecules such as DNA, genes, proteins, cells, and viruses are separated using MNPs.	^{62, 63}
Biofuels	Under an anaerobic environment, Fe NPs favor is the production of biohydrogen.	NPs with a large surface/volume ratio is highly recommendable materials used to produce biofuels and sustainable energy resources providing a higher number of active sites used to catalyze biogas, bioethanol, biohydrogen, and biodiesel.	^64–66
DDS	Pt in conjugation with polymer-coated bioferrofluids acts as antitumor agents against T-cell leukemia and osteosarcoma cells. In immunotherapy, liposomal and polymeric carriers play a major role against tumors.	Due to the superior unique properties of NPs, they have gained core attention in DDS. The NPs based DDS enhances the therapeutic efficacy through various pharmacokinetic, bioavailability properties as it provides slow and controlled release of drugs with better penetration.	^67–69
Chemotherapy	Pt(II) along with Ru or chemical analog-based antimetastatic drug agents has exhibited anticancer properties. Certain AuNPs with various ligands have been studied against human ovarian cancer cells.	NPs have shown a series of advantages to load high yield, targeted delivery, prolonged circulation, and controlled release in DDS. Recently, Au(III), Ru(II), and Pt(II)-based antichemotherapy compounds have reported destroying cancerous cells.	^70–74
Biosensors	The AuNPs carriers-based ELISA signaling antibody was used as a tumor marker to follow up breast cancer and MNPs are used as sensors in NMR, also called DMR.	AuNPs are used in ELISA tests to achieve greater sensitivity. DMR is a successful biosensor technique that offers to profile of cells, DNA, metabolites, and proteins.	^{75, 76}
Immunotherapy	Micelles, carbon NPs, gold NPs, liposomes, QDs, and iron oxide NPs are the widely used nanocarriers as anticancer agents in immunotherapy.	NPs used in combinatorial immunotherapy delivers the drugs effectively to the target sites. Immunotherapy prevents the metastasis and recurrence of tumor cells. NPs can stimulate innate immunity.	^{77, 78}

Abbreviations: CNS, central nervous system; DDS, drug delivery systems; DMR, diagnostic magnetic resonance; ELISA, enzyme linked immunosorbent assay; NMR, nuclear magnetic resonance; NP, nanoparticle; QD, quantum dot; MNP, magnetic NP; PLGA, polymer poly lactic-co-glycolic acid; TiO₂, titanium dioxide; Fe, iron; Pt, platinum; Ru, ruthenium.

The Potential Impacts of Nanotechnology in Various Fields of Biosystem Engineering

Nanotechnology is playing a very important role in functionality development of products and devices by including NPs’ beneficial properties.⁷⁹ However, among several potential nanodevices some are still in the start-up phase while a few devices have already reached the marketing stage.⁵³ Future studies need to be made to check the sustainability, applicability, and efficacy of nanotechnology in comparison with the existing technology.⁵⁴ Following are the impacts of using nanotechnology in various fields of Biosystems engineering.

NPs for Energy Conservation

Conversion of sunlight into electricity is one of the most flexible, interesting renewable technologies.⁵⁵ Graphene,^{56, 57} CNTs,⁵⁸ and C₆₀ fullerenes⁵⁹ are used in quantum dot (QD) and polymer solar cells as efficient electron acceptors. Nanotechnology-based fuel cells are having a high impact on the conversion of chemical energy into electrical energy.⁶⁰ Metals coated onto NPs with low density, high surface area, and chemistry act as the best electrocatalysts for electrode reduction/oxidation reactions in fuel cells.⁶¹ Platinum NPs are regarded to be the best cell catalysts even after they suffer Co deactivation and time-dependent drift.⁶²

NPs for Energy Storage

NPs have also shown a profound activity in electrical storage technologies such as electrochemical supercapacitors and batteries.⁶³ Graphene,⁶⁴ metal oxide NPs such as manganese oxide, ruthenium oxide, iron oxide,⁶⁵ carbon metal oxide,⁶⁶ and CNTs⁶⁷ are aimed at providing high capacity in terms of energy storage. Lithium batteries concerned with performances and energy densities highly depend upon the chemical and physical characteristics of the electrode hence the NPs with a high surface area and reduced dimensions increase the electrode–electrolyte contact and electron transport.⁶⁸

NPs for Biopharmaceuticals

Pharmaceuticals that cannot target can be effectively replaced by a nanotechnology-based drug delivery system.⁶⁹ Usually, 70% to 80% of pharmaceuticals fail in the developmental stage and the failure is often discovered late.⁷⁰ Nanotechnology focuses on developing drugs that target the particular mechanism or site of the disease, and thus the nanoscale technique has become a boon to various companies in drug development.⁷¹ The use of nanotechnology helps in the physical manipulation of the atoms, molecules, and targets by controlling the chemical reactions involved in them.⁷² Hence, this property of NPs results in reduced cost of drug discovery to ease the discovery of new highly specific drugs.⁷³

NPs for Imaging Technique

Intracellular imaging is possible by labeling synthetic chromophores or QDs with target molecules.⁷⁴ Fluorescent proteins through optical techniques can directly investigate and facilitate intracellular signaling using correlation imaging or fluorescence microscopy.⁷⁵

NPs in Drugs and Medication

Nano-sized particles of either simple or complex nature exhibit distinctive physical and chemical properties and signify an ever more essential material in the development of novel nanodevices, which can be used for various physical, biological, biomedical, and pharmaceutical applications.

NPs have drawn growing significance from each field of medicine for their capability to deliver drugs in the optimal dosage range, frequently resulting in increased therapeutic competence of the drugs, weakened side effects, and superior patient observance.⁷⁶

Challenges for Nanotechnology in Biosystem Engineering

Nanotechnology involves major challenges, the first of which is the exposure of animals and humans to the nanomaterials contaminated environment, which needs to be fairly monitored and understood for any adverse consequences.⁷⁷ The second challenge is to determine or detect the toxic effects of NPs caused to the environment and human health by developing different techniques.⁷⁸ Thirdly, a reverse system is in need to measure the impact of NPs on human health and the environment throughout their life span.⁸⁰ The last challenge is to develop techniques to evaluate the risks related to the environment and human health.⁸¹ Scientists all around the world need to develop advanced technology to study regulatory response and risks involved in this area of research (shown in Figure 3).⁸²

Figure 3.

Picture depicting various applications of nanotechnology.

Future Perspectives

Several debates have been raised for developing future implications in nanotechnology. It creates choice and usage of many new materials as potential NPs in the fields of biomaterials, medicine, energy production, and electronics.⁸³ However, this technique will also raise the same issues regarding the impacts of NPs on the environment and their toxicity-related problems. Even after having these disputes, the nanotechnology field has rendered high hopes for the future by playing a prominent role and leading to the innovations of several biomedical techniques, such as biosensors, biomarkers, and molecular imaging to gene therapy and drug delivery.⁸⁴ Advancements in engineered nanotechnology in medicine have led to the opportunity of discovering regenerative medicines and diagnostic techniques to detect diseased cells and stop their further spread to other body parts.

Summary

Nanotechnology for Biosystems engineering is still in the early stage of development. This multidisciplinary area of research is bringing incomprehensive devices to reality. The effects of nanotechnology development are so vast that they might virtually affect the different fields of science and technology. The use of nanodrug delivery systems as therapeutic agents against various diseases should be screened for their safety and risk factors. Henceforth, researchers and scientists are required to focus on the hazardous impact of NPs so that the risk factors can be assessed and prevented. The advancement in this field is very much needed as it possesses a lot of promising benefits over the present technology. Thus, considering these guidelines would help measure further investment and development of engineered products and devices.

Footnotes

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval

Not applicable, because this article does not contain any studies with human or animal subjects.

Informed Consent

Not applicable, because this article does not contain any studies with human or animal subjects.

ORCID iD

Ashajyothi Chavan

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Nanomaterials: Potential Broad Spectrum Antimicrobial Agents

Abstract

Keywords

Introduction

Nanoparticles

NP Size

NP Shape

NP Surface Modification

NP Chemical Composition

Protein Corona

Biosystem Engineering

Applications of Nanotechnology in Biosystem Engineering

The Potential Impacts of Nanotechnology in Various Fields of Biosystem Engineering

NPs for Energy Conservation

NPs for Energy Storage

NPs for Biopharmaceuticals

NPs for Imaging Technique

NPs in Drugs and Medication

Challenges for Nanotechnology in Biosystem Engineering

Future Perspectives

Summary

Footnotes

Declaration of Conflicting Interests

Funding

Ethical Approval

Informed Consent

ORCID iD

References