Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

Infections caused by antibiotic-resistant bacteria continue to challenge the medical field, mostly due to conventional treatments inefficiency after years of overuse and misuse in clinics. Cases of multiresistant bacterial infections are increasing every year. This led the World Health Organization (WHO) to update the list of resistant micro-organisms that represent greatest threat to human health. To stop the growing of the global resistance to antimicrobial drugs, new alternatives are necessary to fight these pathogens. In this context, antimicrobials peptides (AMPs) emerge as a new alternative to the current antibiotics in the pharmaceutical market. To improve their antimicrobial activity, different strategies are being developed to overcome antibiotic-resistant bacteria. Nanotechnology can be used to further potentiate antimicrobials, by increasing their activity or assisting in their delivering, frequently using nanostructured materials. There are already several antimicrobial peptides used in therapeutics, some of them coupled to nanoparticles. Additionally, detection strategies taking advantage of peptides as recognition agents are also being explored. Several examples are detailed of peptides that are specific to bacterial targets, and how that specificity can be used in diagnostics systems, coupled with nanoparticles-based signal detection approaches. Thus, the same properties of AMPs that enable specific neutralization can be harnessed to detect the very same bacteria they target. Overall, this review is focused on current research on nanoparticles coupled to antimicrobial peptides and how they can be used against multidrug-resistant bacteria as antimicrobials and/or as detection system. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

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.

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.

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.

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.

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.

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.

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.

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.