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This book covers the latest information related to understanding immune responses to engineered nanomaterials (ENMs). Many ENMs used in both the consumer and biomedical fields have been reported to elicit adverse immune responses ranging from innate immune responses such as complement activation to changes in adaptive immunity that influence pathogen responses and promote disease states such as asthma. Interaction of Nanomaterials with the Immune System covers the most up to date information on our understanding of immune responses to ENMs across a wide range of topics including innate immunity, allergic immune responses, adaptive provides the reader with (1) up to date understanding of immune responses to ENMs; (2) current testing methods; and (3) appropriate models including alternative testing strategies for evaluating immunotoxicity of ENMs.
The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tilesand masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.
The immune system has the double role of maintaining tissue integrity and homeostasis and of protecting the organism from possible dangers, from invading pathogens to environmentally-borne dangerous chemicals. New chemicals recognisable by the immune system are engineered nanomaterials/ nanoparticles, new agents in our environment that are becoming common due to their presence in many products, from constructions and building material (e.g., solar cells, pigments and paints, tiles and masonry materials) to daily products (e.g., food packaging, cosmetics, and cigarettes). Human beings can be accidentally exposed to engineered nanomaterials when these are released from products containing them or during production in workplaces. Furthermore, intentional exposure occurs in medicine, as engineered nanoparticles are used as tools for improving delivery of drugs and vaccines, vaccine adjuvants and contrast agents in therapeutic, preventive and diagnostic strategies. Nanoparticles that come in contact with the immune system after unintentional exposure need to be eliminated from the organism as they represent a potential threat. In this case, however, due to their peculiar characteristics of size, shape, surface charge and persistence, nanoparticles may elicit undesirable reactions and have detrimental effects on the immune system, such as cytotoxicity, inflammation, anaphylaxis, immunosuppression. Conversely, nanomedicines need to escape immune recognition/elimination and must persist in the organism long enough for reaching their target and exerting their beneficial effects. Immune cells and molecules at the body surface (airway and digestive mucosae, skin) are the first that come in contact with nanomaterials upon accidental exposure, while immune effectors in blood are those that more easily come in contact with nanomedical products. Thus, evaluating the interaction of the immune system with nanoparticles/nanomaterials is a topic of key importance both in nanotoxicology and in nanomedicine. Immuno-nanosafety studies consider both accidental exposure to nanoparticles, which may occur by skin contact, ingestion or inhalation (at doses and with a frequency that are not known), and medical exposure, which takes place with a defined administration schedule (route, dose, frequency). Many studies focus on the interaction between the immune system and nanoparticles that, for medical purposes, have been specifically modified to stimulate immunity or to avoid immune recognition, as in the case of vaccine carriers/adjuvants or drug delivery systems, respectively. The aims of this Research Topic is to provide an overview of recent strategies: 1.for assessing the immunosafety of engineered nanomaterials/nanoparticles, in particular in terms of activation of inflammatory responses, such as complement activation and allergic reactions, based on the nanomaterial intrinsic characteristics and on the possible carry-over of bioactive contaminants such as LPS. Production of new nanoparticles taking into account their effects on immune responses, in order to avoid undesirable effects on one hand, and to design particles with desirable effects for medical applications on the other hand; 2.for designing more effective nanomedicines by either avoiding or exploiting their interaction with the immune systems, with particular focus on cancer diagnosis and therapy, and vaccination. This collection of articles gives a comprehensive view of the state-of-the-art of the interaction of nanoparticles with the immune system from the two perspectives of safety and medical use, and aims at providing immunologists with the relevant knowledge for designing improved strategies for immunologically safe nanomaterial applications.
Nanoparticles and the Immune System provides a reference text for toxicologists, materials scientists and regulators and covers the key issues of interaction of nanomaterials with the immune system. The book discusses several issues that toxicologists and regulators need to know: identification of endpoints that are relevant for assessing hazard, evaluating impact on immunologically frail populations, and how to evaluate chronic/cumulative effects. In addition, the book addresses the possibility of turning the immunomodulating properties of certain nanomaterials to our advantage for amplifying immune responses in certain diseases or preventive strategies (e.g. vaccination). Identifies endpoints relevant for assessing hazardous situations, evaluating the impact on immunologically frail populations and how to gauge chronic/cumulative effects Raises the awareness of the importance of knowing the effects of the new nanomaterials on our immune system
The Handbook of Immunological Properties of Engineered Nanomaterials provides a comprehensive overview of the current literature, methodologies, and translational and regulatory considerations in the field of nanoimmunotoxicology. The main subject is the immunological properties of engineered nanomaterials. Focus areas include interactions between engineered nanomaterials and red blood cells, platelets, endothelial cells, professional phagocytes, T cells, B cells, dendritic cells, complement and coagulation systems, and plasma proteins, with discussions on nanoparticle sterility and sterilization. Each chapter presents a broad literature review of the given focus area, describes protocols and resources available to support research in the individual focus areas, highlights challenges, and outlines unanswered questions and future directions. In addition, the Handbook includes an overview of and serves a guide to the physicochemical characterization of engineered nanomaterials essential to conducting meaningful immunological studies of nanoparticles. Regulations related to immunotoxicity testing of materials prior to their translation into the clinic are also reviewed.The Handbook is written by top experts in the field of nanomedicine, nanotechnology, and translational bionanotechnology, representing academia, government, industry, and consulting organizations, and regulatory agencies. The Handbook is designed to serve as a textbook for students, a practical guide for research laboratories, and an informational resource for scientific consultants, reviewers, and policy makers. It is written such that both experts and beginners will find the information highly useful and applicable.
Nanotechnology is a fast developing area, which refers to research and technology development at the nanometer scale, ranging from 0.1-100 nm. The properties of nanomaterials offer the ability to interact with complex biological functions, implying enormous opportunities for novel applications within medicine. However, there is little information available concerning the potential toxicity of nanoparticles and what influence such particles have on the immune system, e.g. on dendritic cells (DCs). DCs are the most efficient antigen presenting cells, having a capacity to initiate and direct immune responses against foreign material. The aim of this thesis was to study effects of differently sized and shaped nanomaterials in the interaction with primary human monocyte derived DCs (MDDCs), thereby obtaining an insight on what impact these materials have on the immune system and their potential use in medical applications. In addition, we wanted to determine if endogenous nanoparticles (exosomes), produced by various cells, are natural targeting vehicles. We show that conventionally produced gold nanoparticles had a maturing effect on human MDDCs, but this was found to be a result of lipopolysaccharide (LPS) contamination. By modification of the production process, clean particles were obtained, which had practically no effect on phenotype or cytokine production of MDDCs. These findings emphasize the importance of retaining high purity during the production of nanoparticles, since possible contaminants may interfere with the assessment of nanoparticles biological effects and result in hazardous particles. To investigate whether various shapes of gold nanoparticles affect MDDC differently, a novel method was developed for the preparation of gold nanorods with high aspect ratios (ARs) based on a self-seeded surfactant-mediated protocol. The biocompatibility of these high AR gold nanorods, with potential use in thermal therapy, was compared with spherical gold nanoparticles
As nanomaterials become increasingly present in our daily lives, pertinent questions regarding their safety arise. Nanomaterial risk assessment, as in other areas, directs much of the effort worldwide in defining guidelines that may be translated into national or international directives. Nanomaterials encompass different entities, from nanoparticles to nanostructured materials, with specific effects over cells, tissues, organisms and ecosystems depending on their biophysical characteristics. Such interactions will directly affect the impact of novel nanotechnologies. This book aims to provide the reader with a comprehensive overview of the current state of the art in nanotoxicology, featuring the most important developments and critical issues regarding the use of and exposure to nanoparticles.
This unique book provides comprehensive overview of the field of immunology related to engineered nanomaterials used for biomedical applications. It contains literature review, case studies and protocols. The book can serve as a source of information about nanoimmunotoxicology for both junior scientists and experts in the field. The authors have more than 10 years of experience with preclinical characterization of engineered nanomaterials used for medical applications, and they share their experience with the readers. In addition, the international team of experts in the field provides the opinion and share the expertise on individual topics related to nanoparticle physicochemical characterization, hematocompatibility, and effects on the immune cell function . The second edition contains updated chapters from the first edition plus new chapters covering areas of tumor immunology, nanoparticle interaction with lymphatic system, mathematical modeling of protein corona, utilization of nanoparticles for the delivery of antiviral drugs, extensive analysis of nanoparticle anti-inflammatory and immunosuppressive properties, novel ways of protecting therapeutic nanoparticles from the immune recognition, as well as case studies regarding nanoparticle sterilization, complement activation, protein binding and immunotherapy of cancer. The second edition comes in 3 volumes. Volume 1 is focused on nanoparticle characterization, sterility and sterilization, pyrogen contamination and depyrigenation. It also contains overview of regulatory guidelines, protocols for in vitro and in vivo immunotoxicity studies, and correlation between in vitro and in vivo immunoassays. Volume 2 is focused on hematocompatibility of nanomaterials. It provides comprehensive review and protocols for investigating nanoparticle interaction with erythrocytes, platelets, endothelial cells, plasma coagulation factors and plasma proteins forming so called 'corona' around nanoparticles. Volume 3 is dedicated to nanoparticle interaction with and effects on the immune cell function. It also contains examples of nanoparticle use for delivery of antiviral and anti-inflammatory drugs.
The book collects scientific contributions aiming at describing the common mechanism, across living species, by which innate immunity interacts with nanomaterials with the goal of harnessing such interactions for improving environmental and human safety and exploiting them for modulating immunity in vaccination strategies.