The host immune system is highly compromised in case of viral infections and relapses are very common. The capacity of the virus to destroy the host cell by liberating its own DNA or RNA and replicating inside the host cell poses challenges in the development of antiviral therapeutics. In recent years, many new technologies have been explored for diagnosis, prevention, and treatment of viral infections. Nanotechnology has emerged as one of the most promising technologies on account of its ability to deal with viral diseases in an effective manner, addressing the limitations of traditional antiviral medicines. It has not only helped us to overcome problems related to solubility and toxicity of drugs, but also imparted unique properties to drugs, which in turn has increased their potency and selectivity toward viral cells against the host cells. The initial part of the paper focuses on some important proteins of influenza, Ebola, HIV, herpes, Zika, dengue, and corona virus and those of the host cells important for their entry and replication into the host cells. This is followed by different types of nanomaterials which have served as delivery vehicles for the antiviral drugs. It includes various lipid-based, polymer-based, lipid-polymer hybrid-based, carbon-based, inorganic metal-based, surface-modified, and stimuli-sensitive nanomaterials and their application in antiviral therapeutics. The authors also highlight newer promising treatment approaches like nanotraps, nanorobots, nanobubbles, nanofibers, nanodiamonds, nanovaccines, and mathematical modeling for the future. The paper has been updated with the recent developments in nanotechnology-based approaches in view of the ongoing pandemic of COVID-19.Graphical abstract.

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Nanotechnology-based antiviral therapeutics.

The self-assembled layered adsorption of proteins onto nanoparticle (NP) surfaces, once in contact with biological fluids, is termed the "protein corona" and it is gradually seen as a determinant factor for the overall biological behavior of NPs. Here, the previously unreported in vivo protein corona formed in human systemic circulation is described. The human-derived protein corona formed onto PEGylated doxorubicin-encapsulated liposomes (Caelyx) is thoroughly characterized following the recovery of liposomes from the blood circulation of ovarian carcinoma patients. In agreement with previous investigations in mice, the in vivo corona is found to be molecularly richer in comparison to its counterpart ex vivo corona. The intravenously infused liposomes are able to scavenge the blood pool and surface-capture low-molecular-weight, low-abundance plasma proteins that cannot be detected by conventional plasma proteomic analysis. This study describes the previously elusive or postulated formation of protein corona around nanoparticles in vivo in humans and illustrates that it can potentially be used as a novel tool to analyze the blood circulation proteome.

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The Human In Vivo Biomolecule Corona onto PEGylated Liposomes: A Proof-of-Concept Clinical Study

Drug delivery across the blood-brain barrier: recent advances in the use of nanocarriers

In the last ten years, environmental consciousness has increased worldwide, leading to the development of eco-friendly materials to replace synthetic ones. Natural fibers are extracted from renewable resources at low cost. Their combination with synthetic polymers as reinforcement materials has been an important step forward in that direction. The sustainability and excellent physical and biological (e.g., biocompatibility, antimicrobial activity) properties of these biocomposites have extended their application to the biomedical field. This paper offers a detailed overview of the extraction and separation processes applied to natural fibers and their posterior chemical and physical modifications for biocomposite fabrication. Because of the requirements for biomedical device production, specialized biomolecules are currently being incorporated onto these biocomposites. From antibiotics to peptides and plant extracts, to name a few, this review explores their impact on the final biocomposite product, in light of their individual or combined effect, and analyzes the most recurrent strategies for biomolecule immobilization.

https://www.mdpi.com/2218-273X/10/1/148/pdf

Biofunctionalization of Natural Fiber-Reinforced Biocomposites for Biomedical Applications.

Zinc oxide (ZnO) nano/microparticles (NPs/MPs) have been studied as antibiotics to enhance antimicrobial activity against pathogenic bacteria and viruses with or without antibiotic resistance. They have unique physicochemical characteristics that can affect biological and toxicological responses in microorganisms. Metal ion release, particle adsorption, and reactive oxygen species generation are the main mechanisms underlying their antimicrobial action. In this review, we describe the physicochemical characteristics of ZnO NPs/MPs related to biological and toxicological effects and discuss the recent findings of the antimicrobial activity of ZnO NPs/MPs and their combinations with other materials against pathogenic microorganisms. Current biomedical applications of ZnO NPs/MPs and combinations with other materials are also presented. This review will provide the better understanding of ZnO NPs/MPs as antibiotic alternatives and aid in further development of antibiotic agents for industrial and clinical applications.

Antimicrobial Activity of Zinc Oxide Nano/Microparticles and Their Combinations against Pathogenic Microorganisms for Biomedical Applications: From Physicochemical Characteristics to Pharmacological Aspects

Nanotechnology is a multidisciplinary science covering matters involving the nanoscale level that is being developed for a great variety of applications. Nanomedicine is one of these attractive and challenging uses focused on the employment of nanomaterials in medical applications such as drug delivery. However, handling these nanometric systems require defining specific parameters to establish the possible advantages and disadvantages in specific applications. This review presents the fundamental factors of nanoparticles and its microenvironment that must be considered to make an appropriate design for medical applications, mainly: (i) Interactions between nanoparticles and their biological environment, (ii) the interaction mechanisms, (iii) and the physicochemical properties of nanoparticles. On the other hand, the repercussions of the control, alter and modify these parameters in the biomedical applications. Additionally, we briefly report the implications of nanoparticles in nanomedicine and precision medicine, and provide perspectives in immunotherapy, which is opening novel applications as immune-oncology.

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Interactions of Nanoparticles and Biosystems: Microenvironment of Nanoparticles and Biomolecules in Nanomedicine.

Here, cadmium sulphide quantum dots (CdS QDs) have been synthetized and functionalized with Bovine Serum Albumin (BSA) in a colloidal aqueous solution with a stability of over 3 months. Specific synthesis conditions, in homogeneous phase and at low temperature, have allowed limitation of S2− concentration, hence, as a consequence, there is restricted growth of the nanoparticles (NPs). This fact allows binding with BSA in the most favorable manner for the biomolecule. The presence of Cd2+ ions on the surface of the CdS nanoparticle is counteracted by the negatively charged domains of the BSA, resulting in the formation of small NPs, with little tendency for aggregation. Temperature and pH have great influence on the fluorescence characteristics of the synthetized nanoparticles. Working at low temperatures (4 °C) and pH 10–11 have proven the best result as shown by hydrolysis kinetic control of the thioacetamide precursor of S2− ion. Biological activity of the coupled BSA is maintained allowing subsequent bioconjugation with other biomolecules such as antibodies. The chemical conjugation with anti-Glutathione S-transferase (α-GST) antibody, a common tag employed in human recombinant fusion proteins, produces a strong quenching of fluorescence that proves the possibilities of its use in biological labelling. Finally, p53, onco-human recombinant protein (GST tagged in COOH terminus), has been in situ IVTT (in vitro transcription-translation) expressed and efficiently captured by the α-GST-CdS QD conjugate as a proof of the biocompatibility on IVTT systems and the functionality of conjugated antibody.

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Detection of Human p53 In-Vitro Expressed in a Transcription-Translation Cell-Free System by a Novel Conjugate Based on Cadmium Sulphide Nanoparticles.

Gold nanoparticles (AuNPs) have received a special attention in traditional disciplines of analytical chemistry, such as spectroscopy, resulting in powerful tools to improve analytical processes. The motivation of this chapter was to offer a rational vision of the main achievements in the relevant literature according to the use of AuNPs as signal reporters in spectroscopic techniques. Thus, we focus on the use of NPs to improve the detection of chemical and biochemical analytes by various spectroscopic techniques. This chapter has been divided into five sections. The first section is dedicated to the optical characteristics of the AuNPs, which make them suitable as tools in spectroscopic techniques. In the second part, selected works dealing with the use of AuNPs in aggregation-based, surface Plasmon-based, and surface-enhanced Raman spectroscopy-based assays have been critically exposed. The third section focuses on the application of AuNPs in the development of fluorescence methodologies. And in the final two sections, we exposed the uses of AuNPs in phosphorescence processes and chemiluminescence reactions. We chose examples that cover a wide range of methodologies and those that represent new approaches, trying to cover the broad range of analytes. For every example, the analytical principle, the performance, and the application are pointed out. It is important to stand out that the developed techniques with AuNPs offer advantages over the traditional ones, being promising tools to solve present and future analytical challenges. AuNPs are expected to complement or possibly even replace conventional probes and offer great opportunities for advancing fields such as biosensors, molecular imaging, optoelectronics, and nanomedicine.

María Jesús Almendral Parra

Papers

Interactions of Nanoparticles and Biosystems: Microenvironment of Nanoparticles and Biomolecules in Nanomedicine.

Detection of Human p53 In-Vitro Expressed in a Transcription-Translation Cell-Free System by a Novel Conjugate Based on Cadmium Sulphide Nanoparticles.

Spectroscopic Techniques Based on the Use of Gold Nanoparticles