Issues In Nanomedicine Research Articles

Nanozymes for biomedical applications: Multi-metallic systems may improve activity but at the cost of higher toxicity?

Nanozymes are nanomaterials with intrinsic enzyme-like activity with selected advantages over native enzymes such as simple synthesis, controllable activity, high stability, and low cost. These materials have been explored as surrogates to natural enzymes in biosensing, therapeutics, environmental protection, and many other fields. Among different nanozymes classes, metal- and metal oxide-based nanozymes are the most widely studied. In recent years, bi- and tri-metallic nanomaterials have emerged often showing improved nanozyme activity, some of which even possess multifunctional enzyme-like activity. Taking this concept even further, high-entropy nanomaterials, that is, complex multicomponent alloys and ceramics like oxides, may potentially enhance activity even further. However, the addition of various elements to increase catalytic activity may come at the cost of increased toxicity. Since many nanozyme compositions are currently being explored for in vivo biomedical applications, such as cancer therapeutics, toxicity considerations in relation to nanozyme application in biomedicine are of vital importance for translation. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Diagnostic Tools > Diagnostic Nanodevices.

Nanomedicine against biofilm infections: A roadmap of challenges and limitations.

Microbial biofilms are complex three-dimensional structures where sessile microbes are embedded in a polymeric extracellular matrix. Their resistance toward the host immune system as well as to a diverse range of antimicrobial treatments poses a serious health and development threat, being in the top 10 global public health threats declared by the World Health Organization. In an effort to combat biofilm-related microbial infections, several strategies have been developed to independently eliminate biofilms or to complement conventional antibiotic therapies. However, their limitations leave room for other treatment alternatives, where the application of nanotechnology to biofilm eradication has gained significant relevance in recent years. Their small size, penetration efficiency, and the design flexibility that they present makes them a promising alternative for biofilm infection treatment, although they also present set-backs. This review aims to describe the main possibilities and limitations of nanomedicine against biofilms, while covering the main aspects of biofilm formation and study, and the current therapies for biofilm treatment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Water-based technologies for improving water quality at the point of use: A review.

Water safety concerns are increasing tremendously as a result of the rising population and environmental pollution. As a result, viable water treatment approaches need to be designed to meet the water consumption demands of the population, particularly in developing countries. The recent technological advances in water treatment and purification are well articulated in this review. The efficiency of the materials used for purification and their affordability for people living in rural and remote settlements in various parts of the world have been discussed. Water treatment techniques prior to the rapid advancement of science and technology included a variety of strategies such as coagulation/flocculation, filtration, disinfection, flotation and pH correction. The use of nanotechnology in water treatment and purification has modernized the purification process. Therefore, efficient removal of microbes such as bacteria and viruses are exquisitely accomplished. These technologies may include membrane filtration, ultraviolet irradiation, advanced oxidation ion-exchange and biological filtration technologies. Thus, nanotechnology allows for the fabrication of less expensive systems, allowing even low-income people to benefit from it. Most developing countries find these technologies particularly valuable because access to clean and safe water for drinking and residential needs is critical. This is because access to municipal water supplies is also difficult. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Pumped and pumpless microphysiological systems to study (nano)therapeutics.

Fluidic microphysiological systems (MPS) are microfluidic cell culture devices that are designed to mimic the biochemical and biophysical in vivo microenvironments of human tissues better than conventional petri dishes or well-plates. MPS-grown tissue cultures can be used for probing new drugs for their potential primary and secondary toxicities as well as their efficacy. The systems can also be used for assessing the effects of environmental nanoparticles and nanotheranostics, including their rate of uptake, biodistribution, elimination, and toxicity. Pumpless MPS are a group of MPS that often utilize gravity to recirculate cell culture medium through their microfluidic networks, providing some advantages, but also presenting some challenges. They can be operated with near-physiological amounts of blood surrogate (i.e., cell culture medium) that can recirculate in bidirectional or unidirectional flow patterns depending on the device configuration. Here we discuss recent advances in the design and use of both pumped and pumpless MPS with a focus on where pumpless devices can contribute to realizing the potential future role of MPS in evaluating nanomaterials. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Genotoxicity testing of nanomaterials.

Nanomaterials have outstanding and unprecedented advantageous material properties but may also cause adverse effects in humans upon exposure. Testing nanomaterials for genotoxic properties is challenging because traditional testing methods were designed for small, soluble molecules and may not be easily applicable without modifications. This review critically examines available genotoxicity tests for use with nanomaterials, including DNA damage tests such as the comet assay, gene mutation tests such as the mouse lymphoma and hprt assay, and chromosome mutation tests such as the micronucleus test and the chromosome aberration test. It presents arguments for the relative usefulness of various tests, such as preferring the micronucleus test over the chromosome aberration test for scoring chromosome mutations and preferring mammalian cell gene mutation tests because the Ames test has limited utility. Finally, it points out the open questions and further needs in adapting genotoxicity tests for nanomaterials, such as validation, reference nanomaterials, and the selection of top test concentrations, as well as the relevance and applicability of test systems and the need to define testing strategies. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Market entry system considering the biosafety of nanomedical devices in China.

Our current knowledge on nanomaterials is mostly built on data from basic studies, and the application and developmental potentials of nanomaterials are emphasized. On the other hand, standard evaluation methods, models, exposure methods, standards, and guidelines for biological effect evaluation are inadequate. In response to the bottlenecks of supervision, scientific research institutes and regulatory organizations in China have cooperated closely to research and establish an evaluation system for nanomedical devices, and silver-containing nanomaterials have been adopted as an example. In such a context, reference materials, characterization strategies, in vitro and in vivo distribution and toxicity evaluation standards have been established. This article highlights research on the risk assessment of nanomedical device products (taking silver-containing nanomedical device products as an example) in China, including the characterization and release determination strategies, determination of nanosilver in tissues, applications of three-dimensional skin models and in vitro and toxicity evaluation standards have been established. This article highlights research on technical standards. As a consequence, the "Guidelines for the safety and effectiveness evaluation of nanomedical devices" were published in 2021, and a market entry framework for nanomedical devices has been preliminarily formed as a significant component in scientific supervision. This Guideline supervises the review and supervision of nanomedical devices and, therefore, provides a guarantee for the market access of nanomedical devices in China. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Toxicokinetics, dose–response, and risk assessment of nanomaterials: Methodology, challenges, and future perspectives

The rapid growth of nanomaterial applications has raised safety concerns for human health. A number of studies have been conducted to assess the toxicokinetics, toxicology, dose-response, and risk assessment of different nanomaterials using in vitro and in vivo animal and human models. However, current studies cannot meet the demand for efficient assessment of toxicokinetics, dose-response relationships, or the toxicological risk arising from the rapidly increasing number of newly synthesized nanomaterials. In this article, we review the methods for conducting toxicokinetics, hazard identification, dose-response, exposure, and risk assessment studies of nanomaterials, identify the knowledge gaps, and discuss the challenges remaining. We provide the rationale behind the appropriate design of nanomaterial plasma toxicokinetic and tissue distribution studies, including caveats on the interpretation and correlation of in vitro and in vivo toxicology studies. The potential of using physiologically based pharmacokinetic (PBPK) models to extrapolate toxicokinetic and toxicity findings from in vitro to in vivo and from animals to humans is discussed, and the knowledge gaps of PBPK modeling for nanomaterials are identified. While challenges still exist, there has been progress in the toxicokinetics, hazard identification, and risk assessment of nanomaterials in the past two decades. Recent advancements in the field are highlighted with relevant examples. We also share latest guidelines as well as our perspectives on future studies needed to characterize the toxicokinetics, toxicity, and dose-response relationship in support of nanomaterial risk assessment. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Immunotoxicity of nanomaterials in health and disease: Current challenges and emerging approaches for identifying immune modifiers in susceptible populations.

Nanosafety assessment has experienced an intense era of research during the past decades driven by a vivid interest of regulators, industry, and society. Toxicological assays based on in vitro cellular models have undergone an evolution from experimentation using nanoparticulate systems on singular epithelial cell models to employing advanced complex models more realistically mimicking the respective body barriers for analyzing their capacity to alter the immune state of exposed individuals. During this phase, a number of lessons were learned. We have thus arrived at a state where the next chapters have to be opened, pursuing the following objectives: (1) to elucidate underlying mechanisms, (2) to address effects on vulnerable groups, (3) to test material mixtures, and (4) to use realistic doses on (5) sophisticated models. Moreover, data reproducibility has become a significant demand. In this context, we studied the emerging concept of adverse outcome pathways (AOPs) from the perspective of immune activation and modulation resulting in pro-inflammatory versus tolerogenic responses. When considering the interaction of nanomaterials with biological systems, protein corona formation represents the relevant molecular initiating event (e.g., by potential alterations of nanomaterial-adsorbed proteins). Using this as an example, we illustrate how integrated experimental-computational workflows combining in vitro assays with in silico models aid in data enrichment and upon comprehensive ontology-annotated (meta)data upload to online repositories assure FAIRness (Findability, Accessibility, Interoperability, Reusability). Such digital twinning may, in future, assist in early-stage decision-making during therapeutic development, and hence, promote safe-by-design innovation in nanomedicine. Moreover, it may, in combination with in silico-based exposure-relevant dose-finding, serve for risk monitoring in particularly loaded areas, for example, workplaces, taking into account pre-existing health conditions. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Understanding the immunological interactions of engineered nanomaterials: Role of the bio-corona.

Engineered nanomaterials are a broad class of materials with the potential for breakthrough applications in many sectors of society not least in medicine. Consequently, safety assessment of nanomaterials and nano-enabled products with respect to human health and the environment is of key importance. To this end, the biological interactions of nanoscale materials must be understood. Here, the dual "identities" of nanomaterials, namely, the material-intrinsic properties or synthetic identity and the acquired, context-dependent properties or biological identity, are discussed in relation to nanomaterial interactions with the immune system, our main defense against foreign intrusion. Specifically, we address whether macrophages and other innate immune cells respond to the synthetic identity or the biological identity of nanomaterials, that is, the surface adsorbed proteins and/or other biomolecules known as the bio-corona, or both? This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Bismuth nanomaterials as contrast agents for radiography and computed tomography imaging and their quality/safety considerations.

Contrast agents for radiography and computed tomography (CT) scans are substances that can enhance the contrast of blood vessels and soft tissue with detailed imaging information of the diseased sites. However, the large doses, short circulation time and adverse effects are the intrinsic limitations of CT contrast agents, preventing their extended and safe use in the clinical setting. Bismuth nanoparticles (NPs) have gained attention for the high X-ray absorption of bismuth elements with acceptable biocompatibility, showing their potential to be translated into commercialized CT contrast agents. Compared with traditional iodine contrast agents, bismuth NPs are characterized by prolonged circulation time and enhanced contrast, largely due to the surface modification and enhanced permeability and retention effect of NPs. Bismuth NPs can also be flexibly upgraded into sophisticated nanoagents for multimodal imaging and therapeutic purposes by complexation with supporting chemicals, small molecule drugs, fluorescence labels, and other functional agents. Additionally, the affinity and retention of the bismuth NPs in the diseased sites can be further improved by modification of the targeting moiety on the NPs surface. However, a simple synthetic process and low complexity of bismuth NPs are highly recommended for scaling out and quality control of nanoagents with commercialization potential. Since product safety is a prerequisite for the translation of bismuth NPs from bench to the clinic, we focus on recent advances in the distribution, elimination, and toxicity of bismuth NPs previously reported. Finally, we delineate the associated mechanisms for nephrotoxicity and the strategy to reduce the toxicity of bismuth NPs. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

The potential for nanomaterial toxicity affecting the male reproductive system.

With the development of nanotechnology, nanomaterials offer great advantages in a wide variety of industrial and consumer products, and show promise for biomedical applications. However, with these new products, nanomaterial pollutants may enter the human body to cause adverse health effects, including hazards to the male reproductive system. Nanomaterials can enter the body through inhalation, oral exposure, or intravenous injection, and reach the testis via the blood, penetrate the Sertoli cell barrier, and directly or indirectly elicit toxicopathological changes to the testicles. These may then trigger hormone disorders, inhibit spermatogenic cell proliferation, and induce apoptosis, ultimately leading to a decrease in sperm motility and number, ultimately diminishing male reproductive capacity. This review will discuss the toxicological effects of nanomaterials on the male reproductive system, including inflammation, the impact on the hypothalamic-pituitary-gonadal axis (HPG axis), lipid peroxidation, and free ion release relevant to germ cells, Sertoli cell tight junctions, and the gonadal endocrine system. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Predicting nanomaterials pulmonary toxicity in animals by cell culture models: Achievements and perspectives.

Animal experiments are highly relevant models for the assessment of toxicological effects of engineered nanomaterials (ENMs), due to lack of biomonitoring and epidemiological studies. However, the expanding number of ENMs with different physico-chemical properties strains this approach, as there are ethical concerns and economical challenges with the use of animals in toxicology. There is an urgent need for cell culture models that predict the level of toxicological responses in vivo, consequently reducing or replacing the use of animals in nanotoxicology. However, there is still a limited number of studies on in vitro-in vivo correlation of toxicological responses following ENMs exposure. In this review, we collected studies that have compared in vitro and in vivo toxic effects caused by ENMs. We discuss the influence of cell culture models and exposure systems on the predictability of in vitro models to equivalent toxic effects in animal lungs after pulmonary exposure to ENMs. In addition, we discuss approaches to qualitatively or quantitatively compare the effects in vitro and in vivo. The magnitude of toxicological responses in cells that are exposed in submerged condition is not systematically different from the response in cells exposed in air-liquid interface systems, and there appears to be similar ENMs hazard ranking between the two exposure systems. Overall, we show that simple in vitro models with cells exposed to ENMs in submerged condition can be used to predict toxic effects in vivo, and identify future strategies to improve the associations between in vitro and in vivo ENMs-induced pulmonary toxicity. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

The importance of the IL-1 family of cytokines in nanoimmunosafety and nanotoxicology.

Engineered nanomaterials (ENMs) to which humans are exposed intentionally as nanomedicines or unintentionally as invaders, may elicit unforeseen immune reactions. An uncontrollable ENM-induced immune response poses a potential danger to the human body. During an immunological reaction, interleukin (IL)-1 family cytokines, which play key roles under both physiological and pathological conditions, can be secreted by various types of cells into the surrounding environment to induce a series of defensive reactions. However, the crucial roles played by IL-1 family cytokines in ENM-induced immunological responses have not attracted enough attention from researchers to date. In this review, ENM-mediated inflammatory responses and immunotoxicity are discussed, with the main focus directed to IL-1 family cytokines, including IL-1α, IL-1β, IL-1Ra, IL-18, IL-33, IL-36, IL-37, and IL-38. The potential molecular mechanisms of IL-1 family cytokine activity triggered by ENMs, particularly the activation of IL-1α, IL-1β, IL-18, and IL-33, are also reviewed. The understanding of IL-1 family cytokines on nanoimmunosafety provides a fundamental basis for designing safe ENMs that can potentially be used for nanomedicine. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Lipid-based nucleic acid therapeutics with in vivo efficacy.

Synthetic vectors for therapeutic nucleic acid delivery are currently competing significantly with their viral counter parts due to their reduced immunogenicity, large payload capacity, and ease of manufacture under GMP-compliant norms. The approval of Onpattro, a lipid-based siRNA therapeutic, and the proven clinical success of two lipid-based COVID-19 vaccines from Pfizer-BioNTech, and Moderna heralded the specific advantages of lipid-based systems among all other synthetic nucleic acid carriers. Lipid-based systems with diverse payloads-plasmid DNA (pDNA), antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA), small activating RNA (saRNA), and messenger RNA (mRNA)-are now becoming a mature technology, with growing impact in the clinic. Research over four decades identified the key factors determining the therapeutic success of these multi-component systems. Here, we discuss the main nucleic acid-based technologies, presenting their mechanism of action, delivery barriers facing them, the structural properties of the payload as well as the component lipids that regulate physicochemical properties, pharmacokinetics and biodistribution, efficacy, and toxicity of the resultant nanoparticles. We further detail on the formulation parameters, evolution of the manufacturing techniques that generate reproducible and scalable outputs, and key manufacturing aspects that enable control over physicochemical properties of the resultant particles. Preclinical applications of some of these formulations that were successfully translated from in vitro studies to animal models are subsequently discussed. Finally, clinical success and failure of these systems starting from 1993 to present are highlighted, in a holistic literature review focused on lipid-based nucleic acid delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

The critical role of epigenetic mechanisms involved in nanotoxicology.

Over the past decades, nanomaterials (NMs) have been widely applied in the cosmetic, food, engineering, and medical fields. Along with the prevalence of NMs, the toxicological characteristics exhibited by these materials on health and the environment have gradually attracted attentions. A growing number of evidences have indicated that epigenetics holds an essential role in the onset and development of various diseases. NMs could cause epigenetic alterations such as DNA methylation, noncoding RNA (ncRNA) expression, and histone modifications. NMs might alternate either global DNA methylation or the methylation of specific genes to affect the biological function. Abnormal upregulation or downregulation of ncRNAs might also be a potential mechanism for the toxic effects caused by NMs. In parallel, the phosphorylation, acetylation, and methylation of histones also take an important part in the process of NMs-induced toxicity. As the adverse effects of NMs continue to be explored, mechanisms such as chromosomal remodeling, genomic imprinting, and m6 A modification are also gradually coming into the limelight. Since the epigenetic alterations often occur in the early development of diseases, thus the relevant studies not only provide insight into the pathogenesis of diseases, but also screen for the prospective biomarkers for early diagnosis and prevention. This review summarizes the epigenetic alterations elicited by NMs, hoping to provide a clue for nanotoxicity studies and security evaluation of NMs. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Influence of surface chemistry and morphology of nanoparticles on protein corona formation.

Nanomaterials offer promising solutions as drug delivery systems and imaging agents in response to the demand for better therapeutics and diagnostics. However, the limited understanding of the interaction between nanoparticles and biological entities is currently hampering the development of new systems and their applications in clinical settings. Proteins and lipids in biological fluids are known to complex with nanoparticles to form a “biomolecular corona”. This has been shown to affect particles' morphology and behavior in biological systems and their interactions with cells. Hence, understanding how nanomaterials' physicochemical properties affect the formation and composition of this biocorona is a crucial step. This work evaluates existing literature on how morphology (size and shape), and surface chemistry (charge and hydrophobicity) of nanoparticles influence the formation of protein corona. The latest evidence suggest that although surface charge promotes the interaction with proteins and lipids, surface chemistry plays a leading role in determining the affinity of the nanoparticle for biomolecules and, ultimately, the composition of the corona. More recently the study of additional nanoparticles' properties like shape and surface chirality have demonstrated a significant effect on protein corona architecture, providing new tools to tailor biomolecular corona formation.This article is categorized under:Therapeutic Approaches and Drug Discovery > Emerging TechnologiesToxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials

Red blood cells membrane-derived nanoparticles: Applications and key challenges in their clinical translation.

Cellular membrane-derived nanoparticles, particularly of red blood cells (RBCs), represent an emerging class of drug delivery systems. The lack of nucleus and organelles in these cells makes them easy to process and empty out intracellular contents. The empty vesicle membranes can then be either used as a coating on nanoparticles or can be reassembled into a nanovesicle. Engineered RBCs membrane has unique ability to retain its lipid bilayer architecture with host's proteins during top-down approach, thus allowing it to form stable nanoformulations mimicking RBCs stealth properties. In addition, its core-shell structure allows loading of different drug molecules, and its surface chemistry can be manipulated by facile conjugation with ligands on the shell. The remarkable ability of RBCs membrane to fuse with membranes of other cells enables the formation of hybrid nanovesicles. In this review, we highlight the biomedical applications of such vesicles and discuss the potential challenges related to its clinical translation. Although nano-RBCs retain much of the host's proteins, which may give an edge over synthetic nanoparticles in terms of lower immunogenicity, its production at industrial level is more challenging. This review gives the critical analysis of barriers involved in the translation of RBCs-derived nanoparticles from preclinical to clinical level. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.

Baseline and time-updated factors in preclinical development of anionic dendrimers as successful anti-HIV-1 vaginal microbicides.

Although a wide variety of topical microbicides provide promising in vitro and in vivo efficacy, most of them failed to prevent sexual transmission of human immunodeficiency virus type 1 (HIV‐1) in human clinical trials. In vitro, ex vivo, and in vivo models must be optimized, considering the knowledge acquired from unsuccessful and successful clinical trials to improve the current gaps and the preclinical development protocols. To date, dendrimers are the only nanotool that has advanced to human clinical trials as topical microbicides to prevent HIV‐1 transmission. This fact demonstrates the importance and the potential of these molecules as microbicides. Polyanionic dendrimers are highly branched nanocompounds with potent activity against HIV‐1 that disturb HIV‐1 entry. Herein, the most significant advancements in topical microbicide development, trying to mimic the real‐life conditions as closely as possible, are discussed. This review also provides the preclinical assays that anionic dendrimers have passed as microbicides because they can improve current antiviral treatments' efficacy.This article is categorized under:Nanotechnology Approaches to Biology > Nanoscale Systems in BiologyTherapeutic Approaches and Drug Discovery > Nanomedicine for Infectious DiseaseToxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine

Direct nose to the brain nanomedicine delivery presents a formidable challenge.

This advanced review describes the anatomical and physiological barriers and mechanisms impacting nanomedicine translocation from the nasal cavity directly to the brain. There are significant physiological and anatomical differences in the nasal cavity, olfactory area, and airflow reaching the olfactory epithelium between humans and experimentally studied species that should be considered when extrapolating experimental results to humans. Mucus, transporters, and tight junction proteins present barriers to material translocation across the olfactory epithelium. Uptake of nanoparticles through the olfactory mucosa and translocation to the brain can be intracellular via cranial nerves (intraneuronal) or other cells of the olfactory epithelium, or extracellular along cranial nerve pathways (perineural) and surrounding blood vessels (perivascular, the glymphatic system). Transport rates vary greatly among the nose to brain pathways. Nanomedicine physicochemical properties (size, surface charge, surface coating, and particle stability) can affect uptake efficiency, which is usually less than 5%. Incorporation of therapeutic agents in nanoparticles has been shown to produce pharmacokinetic and pharmacodynamic benefits. Assessment of adverse effects has included olfactory mucosa toxicity, ciliotoxicity, and olfactory bulb and brain neurotoxicity. The results have generally suggested the investigated nanomedicines do not present significant toxicity. Research needs to advance the understanding of nanomedicine translocation and its drug cargo after intranasal administration is presented. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials.

Emerging two-dimensional monoelemental materials (Xenes): Fabrication, modification, and applications thereof in the field of bioimaging as nanocarriers.

In recent years, more and more research enthusiasm has been devoted to the development of emerging two-dimensional (2D) monoelement materials (Xenes) and explored potential applications in various fields, especially biomedicine and bioimaging. The inspiring results attribute to their excellent physicochemical properties, including adjustable band gap, surface electronic layout characteristics, and so on, making it easier for surface modification in order to meet designated needs. As a popular interdisciplinary research frontier, a variety of methods for fabricating 2D Xenes have recently been adopted for pre-preparing future practical bioimaging applications, which implies that these materials will have broad clinical application prospects in the future. In this review, we will concentrate on the family of 2D Xenes and summarize their fabrication and modification methods firstly. Then, their applications in bioimaging as nanocarriers will be described according to the Periodic Table of Elements. In addition, current challenges and prospects for further clinical applications will be under discussion and use black phosphorus as a typical example. At last, general conclusion will be made that it is worth expecting that 2D Xenes will play a key role in the next generation of oncologic bioimaging in the future. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.