Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1−100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.

Impact of Nanotechnology on Drug Delivery

Most research on the toxicology of nanomaterials has focused on the effects of nanoparticles that enter the body accidentally. There has been much less research on the toxicology of nanoparticles that are used for biomedical applications, such as drug delivery or imaging, in which the nanoparticles are deliberately placed in the body. Moreover, there are no harmonized standards for assessing the toxicity of nanoparticles to the immune system (immunotoxicity). Here we review recent research on immunotoxicity, along with data on a range of nanotechnology-based drugs that are at different stages in the approval process. Research shows that nanoparticles can stimulate and/or suppress the immune responses, and that their compatibility with the immune system is largely determined by their surface chemistry. Modifying these factors can significantly reduce the immunotoxicity of nanoparticles and make them useful platforms for drug delivery.

Immunological properties of engineered nanomaterials.

Researchers working on the development of vaccines face an inherent dilemma: to maximize immunogenicity without compromising safety and tolerability. Early vaccines often induced long-lived protective immune responses, but tolerability was a major problem. Newer vaccines have very few side effects but can be of limited immunogenicity. One way to tackle this problem is to design vaccines that have all the properties of pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen-associated molecular patterns can be used to induce innate immune responses that promote adaptive immunity. In this Review, we discuss the approaches currently being used to optimize the delivery of antigens and enhance vaccine efficacy.

Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns

Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein ‘corona’. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an ‘adsorbome’ of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein–nanomaterial interactions. We conclude by discussing gaps in the understanding of protein–nanomaterial interactions along with strategies to fill them (167 references).

Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment

Nanoscience has matured significantly during the last decade as it has transitioned from bench top science to applied technology. Presently, nanomaterials are used in a wide variety of commercial products such as electronic components, sports equipment, sun creams and biomedical applications. There are few studies of the long-term consequences of nanoparticles on human health, but governmental agencies, including the United States National Institute for Occupational Safety and Health and Japan's Ministry of Health, have recently raised the question of whether seemingly innocuous materials such as carbon-based nanotubes should be treated with the same caution afforded known carcinogens such as asbestos. Since nanomaterials are increasing a part of everyday consumer products, manufacturing processes, and medical products, it is imperative that both workers and end-users be protected from inhalation of potentially toxic NPs. It also suggests that NPs may need to be sequestered into products so that the NPs are not released into the atmosphere during the product's life or during recycling. Further, non-inhalation routes of NP absorption, including dermal and medical injectables, must be studied in order to understand possible toxic effects. Fewer studies to date have addressed whether the body can eventually eliminate nanomaterials to prevent particle build-up in tissues or organs. This critical review discusses the biophysicochemical properties of various nanomaterials with emphasis on currently available toxicology data and methodologies for evaluating nanoparticle toxicity (286 references).

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Toxicity of nanomaterials

Reference EPFL-CONF-160860View record in Web of Science Record created on 2010-11-30, modified on 2017-05-12

C. P. O"neil

Papers

Exploiting lymphatic transport and complement activation in nanoparticle vaccines