Abstract
The rapid development of nanotechnology has been largely driven by manufacturing of nanoscale particles with specific properties. Until a few years ago, almost no attention had been paid to the potential health risk caused by the aerosolization of engineered nanoparticles, although the health risks associated with incidental and bulk nanoparticles (e.g., diesel particles) had been widely acknowledged and studied. A defining moment came after the nanotechnology consulting firm Lux Research had published a report entitled “Taking action on nanotech environmental, safety and health risks” (2006). The industrial and environmental communities realized the need to identify, characterize, and mitigate exposure to nanoaerosols. At the same time, the medical community made substantial progress in the development of novel approaches for drug/gene/vaccine delivery and molecular imaging methods due to application of nanoparticles. Since then, several valuable review articles and special journal issues have been published on the exposure and health risk associated with nanoparticles (e.g., the 2007 special issue of the Journal of Nanoparticle Research, entitled “Nanoparticles and Occupational Health” and edited by Andrew Maynard and David Pui). However, until now, there have been no attempt to integrate the information about various properties of nanoparticles, their interaction with the lung, and their toxic/therapeutic effects in a fashion offered in the book of Jan Marijnissen and Leon Gradoń.
The book begins with Chapter 1 (by Burtscher), which aims at reviewing the origin of nanoparticles, including combustion processes. Combustion sources generate a considerable number of nanoscale/ultrafine particles, which are sometimes overlooked by investigators because their mass contribution into particular matter measured as PM2.5 and PM10 fractions is usually very small. This fact probably serves as the basis of an arguable conclusion made at the end of Chapter 1 that “most industrial emissions … do not belong to the ultrafine fraction.” Traffic emission is introduced in Chapter 1 as a major source of particles in ambient air, with a large number of particles below 100 nm. As the industrial emissions have been reduced around the globe, at least in the major developed countries, the traffic particulate emission is currently seen as an increasingly important contributor, especially in the nanoscale. The author quotes earlier investigations indicating that 5% of vehicles defined as high emitters (or super polluters) are responsible for more than 40% of the emission. The discussion about characterization of combustion and engine exhaust sources continues in Chapter 2 (by Maricq), which explains the bimodality of particle size distributions typical to combustion-originated aerosols. The first peak is often represented by very small liquid sulfuric acid/hydrocarbon droplets from an engine exhaust (2–20 nm, nucleation mode), whereas the second one is populated primarily by carbonaceous particles (soot) between 10 and 300 nm in diameter. Chapter 2 also addresses the particle charging during combustion; this is an important characteristic that often provides a signature of the particle origin.
Detection and quantification of nanoparticles in the air is a rapidly developing area. Several sophisticated measurement tools have been recently designed and manufactured for studying aerosol particles in the nanoscale. Chapter 6 (by Szymanski and Allmaier) and, partially, Chapter 5 (by Kulmala and Sipilä) provide an extensive review of the methods and techniques utilized for measuring physical properties of aerosol nanoparticles (primarily their size and concentration) in real time. It is noted that no standard procedure has yet been developed in this field. Additionally, Chapter 5 offers an interesting discussion on the formation of “supersmall” aerosol nanoparticles and their filtration. Both issues are relevant to the development of appropriate measurement capabilities, especially for particle sizes that fall in a range of 1 to 10 nm.
The generation of nanoparticles for medical applications is discussed in two chapters. Marijnissen et al. (Chapter 3) introduced ElectroHydrodynamic Atomization (EHDA), conventionally called “electrospray,” as an approach with good potential for producing particles that can meet challengers of biomedical applications. Utilization of EHDA is being presently explored for generation of charged and noncharged monodisperse droplets with minimum impurities, controlled porosity and shape, and ability to be deposited on different carriers. Discussion regarding the slow release and low-density particles is of special interest. Chen and Pui (Chapter 4) address the application of Single- and Dual-Capillary electrospray techniques for generating nanoparticles that are intended to be used in medical and biological applications. The authors demonstrate advantages of electrospray-produced particles of various shapes for coating of medical devices and inhaler-based drug delivery. Additionally, Chapter 4 describes the possibility of utilizing the nanogradient growth factor for guided neuron growth. Applications of nanoparticles for coating of intravascular stents and gene delivery are also discussed. In this chapter, Chen and Pui address an important issue of viability of biomaterials that can be incorporated in nanoparticles. Degradation of biomaterials such as enzymes or cytokines upon generation of nanoparticles represents a challenge that is often underestimated.
Some interesting aspects of quantum chemical calculations, including those applicable to drug design, are discussed in Chapter 9. The authors, Brocklawik and Uvarova, present an introduction to the emerging field of computational medicinal chemistry and discuss a broad range of biomedically relevant issues. Although this chapter stands somewhat apart from the overall theme, it certainly adds to the book's value.
Inhalation and deposition of nanoparticles in the human respiratory system is a very important area for establishing exposure–health relationships. Chapter 7 (by Moskal et al.) presents a number of basic equations from fluid and aerosol mechanics, which allow quantifying the particle movement in the upper and lower airways and ultimately help determining the dose. Chapter 8 (by Kreyling and Geider) discusses dosimetry that “comprises the deposition behavior of inhaled particles and their biokinetics fate in the respiratory tract and in the entire organism.” The information described in this chapter is especially important because dosimetry is a critical component in the health risk identification and quantification. A comprehensive review of the nanoparticle dosimetry offered by the authors makes this chapter one of the centerpieces of the book.
Baughman and Pirozynski discussed health effects of inhaled nanoparticles from a therapy/toxicity prospective (Chapter 10). Multiple studies have established associations between ultrafine particles (e.g., diesel exhaust particles) and respiratory health effects, including those linked to the lung development and function. Prolonged exposure to ultrafine particles may lead to serious lung dysfunction, including severe asthma, bronchiolitis, sarcoidosis, chronic obstructive pulmonary disease (COPD), and other conditions. The authors of Chapter 10 address toxicity and safety issues in the context of therapeutical application of nanoparticles. Despite legitimate safety concerns, inhalation of nanoparticles is still considered a promising method for drug delivery in pulmonary medicine.
Chapter 11 (by Hiemistra) provides an insight in effects of diesel particles and cigarette smoke on functions of innate immune system. This chapter fills some gaps in understanding how these pollutants affect the lung epithelium and immune cells, particularly upon respiratory infections and chronic lung diseases. Exposure to toxic ultrafine particles can significantly contribute to the development of lung inflammation. Possibly, it occurs via activation of pattern recognition receptors that lead to increased mucus production, pro-inflammatory release of cytokines (IL-6, TNF-α, etc.) and chemokines (CC16, CCR3, etc.), and impairment of homeostatic balance in lungs. All the above may significantly worsen acute or chronic pulmonary diseases. While offering an extensive discussion about health risks associated with exposure to smoke and diesel exhaust, the chapter also refers to the studies that show an immunosuppressive effect of these pollutants. The author concludes that the interaction of smoke and diesel particles with specific components of the immune system needs to be further investigated.
Potentially harmful and beneficial effects of nanoparticles in children are discussed in Chapter 12 (by Schüepp). The author stated that developmental stage, immature enzyme system, and increased activity of children make them particularly vulnerable to toxic nanoparticles exposure. On the contrary, the children's lungs are relatively resistant to inhalation due to accelerated clearance. Nanoparticle application in children may be particularly beneficial for enhancing the drug delivery and vaccination. An extensive list of references presented in this chapter provides a great opportunity for the readers to expand their knowledge on some issues that have been only briefly addressed in this chapter.
Chapter 13 (Häusserman et al.) is concerned with the targeting drug delivery. As an example, the authors discuss the aerosol-based insulin inhalation therapy. Applications of commercially available inhaler-based insulin treatments are reviewed; benefits and challenges of the lung-targeted fine particle-based therapies are discussed. Advantages of inhaler-based insulin therapy include rapid adsorption and hypoglycemic effect, which may be achieved faster than upon subcutaneous injections. In addition, easy and less harmful inhaler-based insulin application has a significant advantage over numerous subcutaneous insulin injections. The above features allow generating sophisticated systems that are good enough to advance to phase III clinical trials. There are still a significant number of open questions. Age, gender, and physiological conditions such as asthma, COPD, and history of smoking can affect pharmacokinetics of inhaled insulin. Moreover, the lungs are evolutionary maintained as a sterile environment strongly protected by innate and adaptive immune system. Repeated multiple inhalations of nonself-proteins can induce immune and autoimmune responses that result in serious side effects up to IgE- and IgG-mediated anaphylaxis. On the contrary, inhalation of aerosols for vaccination purposes or for lung-targeted applications such as for lung cancer treatment may be very beneficial. Other routes of nanoparticles delivery is presently under investigation. The authors stated that more studies are needed to elucidate complex and important issues such as toxicity/safety, modulation of host defense system, pharmacokinetics, and others. These can lead to fascinating discoveries and a new generation of valuable therapeutic applications.
To reduce inhalation exposure to airborne nanoparticles, different stationary and individual respiratory protection methods can be deployed. Most of these methods utilize aerosol filtration, primarily through diffusion and electrostatic mechanisms. A classic theory of aerosol filtration and its applications for nanoparticles, as well as recently reported experimental data, are incorporated in Chapter 14 (by Podġorski). In our opinion, this short review on the topic is a great contribution to the book that may equally serve beginners and experts in the field.
The last chapter of the book (by Marijnissen et al.) offers a great “executive summary” integrating various issues described in specific chapters and raising additional questions regarding the characterization of environmental and medicinal nanoparticles with a focus on their inhalation, respiratory deposition, and health effects. Chapter 15 also paves the road to future endeavors in these research areas.
If there are shortcomings, they are rather minor. The wealth of information presented in this book, requires, in our opinion, a far more comprehensive index than provided. In several chapters, the references are not completely up to date. Some topics clearly received less attention than others. A separate chapter on nanoparticles of biological origin (nanobioaerosols) could have been considered. However, our overriding conclusion is that the above critique has no major impact on the scientific content or structure of the book.
Aimed at a broad readership—from graduate-level students to established researchers—this almost 300-page book represents an important contribution to the field. Although it covers a rather broad territory, the book apparently did not intend to be a comprehensive source of information about nanoparticles. This does not make it less valuable. The breadth of the subject makes it unrealistic to expect a reader to be necessarily interested in all the topics addressed in the book; however, the individual chapters are useful and informative on a wide range of topics. In most instances, the authors and the editors managed to communicate complex matters skillfully. To some extent, this is achieved due to numerous figures presenting various schematics as well as graphs loaded with original scientific data.
Any book that features a collection of articles written by participants of a scientific meeting reflects the profile of the group. The book “Nanoparticles in Medicine and Environment” is no exception. Considering the multidisciplinary research expertise of the workshop participants, the profile of this group is truly diverse (if not to say eclectic). From this perspective, the editors should be given special credit for the maintaining structure and ideological integrity of the book.
To summarize, we enjoyed the book and highly recommend it to the readers of the Journal of Aerosol Medicine as well as to a broader professional community working in environmental science, epidemiology, different areas of biomedical research (e.g., drug/gene/vaccine delivery and molecular imaging), and other relevant areas.