Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

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 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.

In recent years, there have been significant innovations in the development of nanoparticle-based vaccines and vaccine delivery systems. For the purposes of both design and evaluation, these nanovaccines are imaged using the wealth of understanding established around medical imaging of nanomaterials. An important insight to the advancement of the field of nanovaccines can be given by an analysis of the design rationale of an imaging platform, as well as the significance of the information provided by imaging. Nanovaccine imaging strategies can be categorized by the imaging modality leveraged, but it is also worth understanding the superiority or convenience of a given modality over others in a given context of a particular nanovaccine. The most important imaging modalities in this endeavor are optical imaging including near-infrared fluorescence imaging (NIRF), emission tomography methods such as positron emission tomography (PET) and single photon emission computed tomography (SPECT) with or without computed tomography (CT) or magnetic resonance (MR), the emerging magnetic particle imaging (MPI), and finally, multimodal applications of imaging which include molecular imaging with magnetic resonance imaging (MRI) and photoacoustic (PA) imaging. One finds that each of these modalities has strengths and weaknesses, but optical and PET imaging tend, in this context, to be currently the most accessible, convenient, and informative modalities. Nevertheless, an important principle is that there is not a one-size-fits-all solution, and that the specific nanovaccine in question must be compatible with a particular imaging modality. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.

Laser interstitial thermal therapy (LITT) guided by magnetic resonance imaging (MRI) is a new treatment option for patients with brain and non-central nervous system (non-CNS) tumors. MRI guidance allows for precise placement of optical fiber in the tumor, while MR thermometry provides real-time monitoring and assessment of thermal doses during the procedure. Despite promising clinical results, LITT complications relating to brain tumor procedures, such as hemorrhage, edema, seizures, and thermal injury to nearby healthy tissues, remain a significant concern. To address these complications, nanoparticles offer unique prospects for precise interstitial hyperthermia applications that increase heat transport within the tumor while reducing thermal impacts on neighboring healthy tissues. Furthermore, nanoparticles permit the co-delivery of therapeutic compounds that not only synergize with LITT, but can also improve overall effectiveness and safety. In addition, efficient heat-generating nanoparticles with unique optical properties can enhance LITT treatments through improved real-time imaging and thermal sensing. This review will focus on (1) types of inorganic and organic nanoparticles for LITT; (2) in vitro, in silico, and ex vivo studies that investigate nanoparticles' effect on light-tissue interactions; and (3) the role of nanoparticle formulations in advancing clinically relevant image-guided technologies for LITT. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery.

Despite current advances in new approaches for cancer detection and treatment, pancreatic cancer remains one of the most lethal cancer types. Difficult to detect early, aggressive tumor biology, and resistance to chemotherapy, radiotherapy, and immunotherapy result in a poor prognosis of pancreatic cancer patients with a 5-year survival of 10%. With advances in cancer nanotechnology, new imaging and drug delivery approaches that allow the development of multifunctional nanotheranostic agents offer opportunities for improving pancreatic cancer treatment using precision oncology. In this review, we will introduce potential applications of innovative theranostic strategies to address major challenges in the treatment of pancreatic cancer at different disease stages. Several important issues concerning targeted delivery of theranostic nanoparticles and tumor stromal barriers are discussed. We then focus on the development of a magnetic iron oxide nanoparticle platform for multimodal therapy of pancreatic cancer, including MRI monitoring targeted nanoparticle/drug delivery, therapeutic response, and tumor re-staging, activation of tumor immune response by immunoactivating nanoparticle and magnetic hyperthermia therapy, and intraoperative interventions for improving the outcome of targeted therapy. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Enzyme-mediated intratumoral self-assembled (EMISA) nanotheranostics represent a new class of smart agents for combined imaging and therapy of cancer. Cancer cells overexpress various enzymes that are essential for high metabolism, fast proliferation, and tissue invasion and metastasis. By conjugating small molecules that contain an enzyme-specific cleavage site to appropriate chemical linkers, it is possible to induce self-assembly of nanostructures in tumor cells having the target enzyme. This approach of injecting small theranostic molecules that eventually become larger nanotheranostics in situ avoids some of the major limitations that are encountered when injecting larger, pre-assembled nanotheranostics. The advantage of EMISA nanotheranostics include the avoidance of nonspecific uptake and rapid clearance by phagocytic cells, increased cellular accumulation, reduced drug efflux and prolonged cellular exposure time, all of which lead to an amplified imaging signal and therapeutic efficacy. We review here the different approaches that can be used for preparing EMISA-based organic, inorganic, or organic/inorganic hybrid nanotheranostics based on noncovalent interactions and/or covalent bonding. Imaging examples are shown for fluorescence imaging, nuclear imaging, photoacoustic imaging, Raman imaging, computed tomography imaging, bioluminescent imaging, and magnetic resonance imaging. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Biology-Inspired Nanomaterials > Peptide-Based Structures.

Continuous long-term intracellular imaging and multiplexed monitoring of biomolecular changes associated with key cellular processes remains a challenge for the scientific community. Recently, surface-enhanced Raman scattering (SERS) has been demonstrated as a powerful spectroscopic tool in the field of biology owing to its significant advantages. Some of these include the ability to provide molecule-specific information with exquisite sensitivity, working with small volumes of precious samples, real-time monitoring, and optimal optical contrast. More importantly, the availability of a large number of novel Raman reporters with narrower full width at half maximum (FWHM) of spectral peaks/vibrational modes than conventional fluorophores has created a versatile palette of SERS-based probes that allow targeted multiplex sensing surpassing the detection sensitivity of even fluorescent probes. Due to its nondestructive nature, its applicability has been recognized for biological sensing, molecular imaging, and dynamic monitoring of complex intracellular processes. We critically discuss recent developments in this area with a focus on different applications where SERS has been used for obtaining information that remains elusive for conventional imaging methods. Current reports indicate that SERS has made significant inroads in the field of biology and has the potential to be used for in vivo human applications. This article is categorized under: Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Surface-enhanced Raman spectroscopy (SERS) is an emerging powerful vibrational technique offering unprecedented opportunities in biomedical science for the sensitive detection of biomarkers and the imaging and tracking of biological samples. Conventional SERS detection is based on the use of plasmonic substrates (e.g., Au and Ag nanostructures), which exhibit very high enhancement factors (EF = 10¹⁰ -10¹¹ ) but suffers from serious limitations, including light-induced local heating effect due to ohmic loss and expensive price. These drawbacks may limit detection accuracy and large-scaled practical applications. In this review, we focus on alternative approaches based on plasmon-free SERS detection on low-cost nanostructures, such as carbons, oxides, chalcogenides, polymers, silicons, and so forth. The mechanism of non-plasmonic SERS detection has been attributed to interfacial charge transfer between the substrate and the adsorbed molecules, with no photothermal side-effects but usually less EF compared with plasmonic nanostructures. The strategies to improve Raman signal detection, through the tailoring of substrate composition, structure, and surface chemistry, is reviewed and discussed. The biomedical applications, for example, SERS cell characterization, biosensing, and bioimaging are also presented, highlighting the importance of substrate surface functionalization to achieve sensitive, accurate analysis, and excellent biocompatibility. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > Biosensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.