The role of high-resolution imaging in the evaluation of nanosystems for bioactive encapsulation and targeted nanotherapy

Nanotechnology has already started to significantly impact many industries and scientific fields including biotechnology, pharmaceutics, food technology and semiconductors. Nanotechnology-based tools and devices, including high-resolution imaging techniques, enable characterization and manipulation of materials at the nanolevel and further elucidate nanoscale phenomena and equip us with the ability to fabricate novel materials and structures. One of the most promising impacts of nanotechnology is in the area of nanotherapy. Employing nanosystems such as dendrimers, nanoliposomes, niosomes, nanotubes, emulsions and quantum dots, nanotherapy leads toward the concept of personalized medicine and the potential for early diagnoses coupled with efficient targeted therapy. The development of smart targeted nanocarriers that can deliver bioactives at a controlled rate directly to the designated cells and tissues will provide better efficacy and reduced side effects. Nanocarriers improve the solubility of bioactives and allow for the delivery of not only small-molecule drugs but also the delivery of nucleic acids and proteins. This review will focus on nanoscale bioactive delivery and targeting mechanisms and the role of high-resolution imaging techniques in the evaluation and development of nanocarriers.     

The long view of nanotechnology development: the National Nanotechnology Initiative at 10 years

A global scientific and societal endeavor was set in motion by the nanotechnology vision formulated in 1999 that inspired the National Nanotechnology Initiative (NNI) and other national and international R&D programs. Establishing foundational knowledge at the nanoscale has been the main focus of the nanotechnology research community in the first decade. As of 2009, this new knowledge underpinned about a quarter of a trillion dollars worldwide market, of which about $91 billion was in US products that incorporate nanoscale components. Nanotechnology is already evolving toward becoming a general-purpose technology by 2020, encompassing four generations of products with increasing structural and dynamic complexity: (1) passive nanostructures, (2) active nanostructures, (3) nanosystems, and (4) molecular nanosystems. By 2020, the increasing integration of nanoscale science and engineering knowledge and of nanosystems promises mass applications of nanotechnology in industry, medicine, and computing, and in better comprehension and conservation of nature. Nanotechnology’s rapid development worldwide is a testimony to the transformative power of identifying a concept or trend and laying out a vision at the synergistic confluence of diverse scientific research areas. This chapter provides a brief perspective on the development of the NNI since 2000 in the international context, the main outcomes of the R&D programs after 10 years, the governance aspects specific to this emerging field, lessons learned, and most importantly, how the nanotechnology community should prepare for the future.     

Measurement of nanomechanical properties of biomolecules using atomic force microscopy

The capabilities of atomic force microscopy (AFM) have been rapidly expanding beyond topographical imaging to now allow for the analysis of a wide range of properties of diverse materials. The technique of nanoindentation, traditionally performed via dedicated indenters can now be reliably achieved using AFM instrumentation, enabling mechanical property determination at the nanoscale using the high spatial and force resolutions of the AFM. In the study of biological systems, from biomolecules to complexes, this technique provides insight into how mesoscale properties and functions may arise from a myriad of single biomolecules. In vivo and in situ analyses of native structures under physiological conditions as well as the rapid analysis of molecular species under a variety of experimental treatments are made possible with this technique. As a result, AFM nanoindentation has emerged as a critical tool for the study of biological systems in their natural state, further contributing to both biomaterial design and pharmacological research. In this review, we detail the theory and progression of AFM-based nanoindentation, and present several applications of this technique as it has been used to probe biomolecules and biological nanostructures from single proteins to complex assemblies. We further detail the many challenges associated with mechanical models and required assumptions for model validity. AFM nanoindentation capabilities have provided an excellent improvement over conventional nanomechanical tools and by integration of topographical data from imaging, enabled the rapid extraction and presentation of mechanical data for biological samples.     

Multidimensional magnesium oxide nanostructures with cone-shaped branching

Branching structures in nanometer level are of great importance in developing nanoscale science and functional electrical devices. In this letter, multidimensional magnesium oxide structures with cone-shaped branching have been mass-produced using a simple chemical vapor deposition method. The dominant structures in the product include two-dimensional ‘+’, ‘T’, or ‘Γ’ assemblies, and three-dimensional complex configurations. The results presented here enrich the nanoscale community with new basic materials for the fabrication of functional electrical and chemical sensing devices.     

International perspective on nanotechnology papers,patents, and NSF awards (2000–2016)

This paper presents the development of nanotechnology between 2000 and 2016 as reflected in the Web of Science papers, United States Patent and Trademark Office (USPTO), World International Property Organization (WIPO) patents, and National Science Foundation (NSF) awards, with a special reference to the United States (US), European Union (EU27), P.R. China, Japan, and South Korea. The field of nanotechnology is branching out into novel scientific and technology platforms, and it is increasingly difficult to separate foundational nanoscale components from divergent application areas. The average global growth rate has been sustained at about 15% for both papers and patents in the selected interval. The growth rates among regions are non-uniform. P.R. China and South Korea have increased faster in both the numbers and quality of their scientific publications, and currently P.R. China has the largest volume of nanotechnology publications and South Korea the most publications per capita in the field of nanotechnology. The US, EU27, and Japan are maintaining leadership in the upstream, better cited, conceptual components of nanotechnology research and development.     

Clinical Plasma Medicine: State and Perspectives of in Vivo Application of Cold Atmospheric Plasma

Driven by extensive basic research on plasma effects on living cells and microorganisms, plasma medicine has been developed as innovative medical research field during the last years. Besides partially established applications of plasma to treat materials or devices to allow effective medical applications with respect to biocompatibility or microbiological safety, respectively, the primary focus of plasma‐medical research is the direct application of plasma as part of therapeutic concepts. Even if a huge number of atmospheric pressure plasma sources for biomedical applications are described in the literature and characterized by in vitro microbiology and cell biology, there is only a limited number of in vivo experience with animals or human beings up to now. Research in plasma medicine has been mainly focused on applications in dermatology and aesthetic surgery with the aim to support tissue regeneration to improve healing of infected and/or chronic wounds as well as to treat infective and inflamed skin diseases. In general, there are four cold atmospheric plasma sources which were tested comprehensively in animals as well as human beings with respect both to its therapeutic potential and the safety of its application. Three clinical trials with cold atmospheric pressure plasma sources have been carried out yet. All three studies realized in Germany are focused on ulcer treatment. Two cold atmospheric pressure plasma sources got a CE marking as medical device in 2013. This marks a very important step to bring plasma medicine into the clinical daily routine! In future, it will become a general practical requirement to adapt special plasma sources to specific medical applications. Consequently, it is one of the main requirements for the physical and technical field of research and development in plasma medicine to find solutions for modular and flexible plasma devices which are adaptive to some extent e.g. to variable target areas. Based on this as well as together with comprehensive basic research to get much more insight into detailed mechanisms of plasma‐induced effects on living structures and the particular role of single plasma components, further fields of plasma application in vivo will be opened or extended, respectively, with both new targets like cancer treatment or new application sites like teeth, lung, eyes, nasal cavity or gastrointestinal tract. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A review on techniques to fabricate silicon oxide arrays for biomolecules patterning

The development of methods for pattern proteins and other functional molecules on the surfaces with nanoscale accuracy is indispensable to take advantage of their properties in ultrasensitive and/or high-density devices. Several methods are used to fabricate organized micro/nanohierarchical structures on a surface and give the ability of molecules to self-assemble by using the mutual recognition properties. However, the supramolecular organization is difficult to extend from nano- to mesoscopic length scales or does not allow accurate placement of the desired structures on a specific region of an inhomogeneous surface. This paper reviews the different techniques used to fabricate nano/millimeter range patterns on SiO₂/Si substrates and local chemical grafting to perform successful attachment of biomolecules on predetermined areas.     

Scanning probe microscopies, nanoscience and nanotechnology

The symbiotic relationship between nanoscience and nanotechnology and the scanning probe microscopies is analyzed in terms of relating non-contact atomic force microscope (NC-AFM) technology to applications requiring detection, manipulation and fabrication on the molecular scale. The features of NC-AFM in this connection, which facilitate its unique relationship with nanoscale science and technology, are discussed. Specific typical examples are presented of applications where a NC-AFM measurement of a specific physical or chemical property is correlated with position, orientation or location on the atomic scale.     

Anticipatory Standards and the Commercialization of Nanotechnology

Standardization will play an increasing role in creating a smooth transition from the laboratory to the marketplace as products based on nanotechnology are developed and move into broad use. Traditionally, standards have evolved out of a need to achieve interoperability among existing products, create order in markets, simplify production and ensure safety. This view does not account for the escalating trend in standardization, especially in emerging technology sectors, in which standards working groups anticipate the evolution of a technology and facilitate its rapid development and entrée to the market place. It is important that the nanotechnology community views standards as a vital tool to promote progress along the nanotechnology value chain – from nanoscale materials that form the building blocks for components and devices to the integration of these devices into functional systems.This paper describes the need for and benefits derived from developing consensus standards in nanotechnology, and how standards are created. Anticipatory standards can nurture the growth of nanotechnology by drawing on the lessons learned from a standards effort that has and continues to revolutionize the telecommunications industry. Also, a brief review is presented on current efforts in the US to create nanotechnology standards.     

Stickiness of the Hydrogen Bond

The dielectric response of bulk water follows laws of continuum electrostatics, a scheme often extrapolated without justification to treat confined interfacial water, where the Debye polarization ansatz breaks down and discrete effects matter. Reconciling the discrete behavior with the continuum equations requires a conceptual leap, all the more so when assessing the electrostatic impact of exclusion of individual water molecules. This work takes up the challenge and identifies the nanoscale stickiness of a preformed water‐embedded hydrogen bond as phenomena not encompassed by continuum laws but quantitatively predictable when adopting a nanoscale theory of dielectric response holding down to molecular dimensions. Nanoscale stickiness is known to drive basic cellular events and has been measured using a molecular force probe but its physical underpinnings and computation have been lacking so far. The findings reported may impact molecular design in bio‐nanotechnology and shed light on standing challenges in biophysics, especially on the protein folding problem, where organized compaction of the protein chain following nucleating intramolecular hydrogen bonding demands explanation.     

Dynamic mechanism of HIV replication inhibitor peptide encapsulated into carbon nanotubes

Biomolecules encapsulated in carbon nanotubes (CNTs) have attracted much interest and facilitated exciting opportunities for biological and biomedical applications of CNTs. Understanding the fundamental interaction and change in biomolecules during encapsulation is indispensable but remains a challenge for both theoretical and experimental investigations. This paper focuses on the interaction between HIV replication inhibitor peptide (HRIP) and CNTs in a neutral solution with molecular dynamics simulation. We observed that HRIP spontaneously inserts into the CNTs and oscillates around the center of the tube, where the non-covalent interaction is minimum. The effects of the diameters of the CNTs on HRIP were investigated. The optimal diameter of the CNT that can provide the most effective encapsulation and causes minimum conformational change in HRIP was found. The present results provide valuable insights in the understanding of nanoscale drug delivery using CNT-based devices.     

毛细管电泳-原子光(质)谱联用技术在金属形态与生物分子相互作用研究中的应用

金属形态与生物分子相互作用研究对于揭示金属元素在正常生命过程、重大疾病的发生、诊断和治疗过程中的作用机理具有重要意义,发展研究金属元素形态与生物活性分子相互作用的新技术和新方法非常重要。简要总结了十余年来,在发展毛细管电泳与电热原子吸收光谱和毛细管电泳与电感耦合等离子体质谱在线联用新技术,及其在不同形态金属与生物分子相互作用机理研究方面的工作。这些工作利用毛细管电泳-原子光(质)谱联用技术不仅能够直接证明镉、锌、不同形态的汞、不同形态的锑与谷胱甘肽、DNA、人血清白蛋白、牛血清白蛋白间的相互作用,以及这些金属及其不同形态与生物分子加合物的生成,而且还能够测定相互作用的热力学参数、反应级数和动力学参数。另外,结合圆二色光谱、红外光谱光谱、拉曼光谱和X射线光电子能谱等实验手段,进一步研究了金属及其不同形态与生物分子作用对生物分子二级结构的影响及在生物分子上可能的结合位点等。     

Plasmas for medicine

Plasma medicine is an innovative and emerging field combining plasma physics, life science and clinical medicine. In a more general perspective, medical application of physical plasma can be subdivided into two principal approaches. (i) “Indirect” use of plasma-based or plasma-supplemented techniques to treat surfaces, materials or devices to realize specific qualities for subsequent special medical applications, and (ii) application of physical plasma on or in the human (or animal) body to realize therapeutic effects based on direct interaction of plasma with living tissue. The field of plasma applications for the treatment of medical materials or devices is intensively researched and partially well established for several years. However, plasma medicine in the sense of its actual definition as a new field of research focuses on the use of plasma technology in the treatment of living cells, tissues, and organs. Therefore, the aim of the new research field of plasma medicine is the exploitation of a much more differentiated interaction of specific plasma components with specific structural as well as functional elements or functionalities of living cells. This interaction can possibly lead either to stimulation or inhibition of cellular function and be finally used for therapeutic purposes. During recent years a broad spectrum of different plasma sources with various names dedicated for biomedical applications has been reported. So far, research activities were mainly focused on barrier discharges and plasma jets working at atmospheric pressure.     

Imaging and manipulation of biological structures with the AFM

Many biologists have dreamt of physically touching and manipulating the biomolecules they were investigating. With the invention of the atomic force microscope (AFM), this dream has come true. Here, recent applications of the AFM to image and to manipulate biological systems at the nanometer scale are reviewed. Macromolecular biological assemblies as well as individual biomolecules can be subjected to controlled nanomanipulation. Examples of AFM application in imaging and nanomanipulation include the extraction of chromosomal DNA for genetic analysis, the disruption of antibody--antigen bonds, the dissection of biological membranes, the nanodissection of protein complexes, and the controlled modulation of protein conformations. Also reviewed is the novel combination of single molecule imaging and force spectroscopy which allows biomolecules to be imaged, and inter- and intramolecular forces to be measured. Future application of these nanotechniques will reveal new information on the structure, function and assembly of biomolecules.     

Current nanoscience and nanoengineering at the Center for Nanoscale Science and Engineering

The Center for Nanoscale Science and Engineering (CeNSE) at the University of Kentucky is a multidisciplinary group of faculty, students, and staff, with a shared vision and cutting-edge research facilities to study and develop materials and devices at the nanoscale. Current research projects at CeNSE span a number of diverse nanoscience thrusts in bio-engineering and medicine (nanosensors and nanoelectrodes, nanoparticle-based drug delivery), electronics (nanolithography, molecular electronics, nanotube FETs), nanotemplates for electronics and gas sensors (functionalization of carbon nanotubes, aligned carbon nanotube structures for gate-keeping, e-beam lithography with nanoscale precision), and nano-optoelectronics (nanoscale photonics for laser communications, quantum confinement in photovoltaic devices, and nanostructured displays). This paper provides glimpses of this research and future directions.     

Characterization of Nanophase Materials

This contribution is a preprint of one chapter of Professor Wang's edited new book “Characterization of Nanophase Materials” (ISBN 3–527–29837–1), published by WILEY–VCH Verlag GmbH, Weinheim, Germany. Engineering of nanophase materials and devices is of vital interest in electronics, semiconductors and optics, catalysis, ceramics and magnetism. Development of nanotechnology involves several steps, of which characterization of nanoparticles is indespensable in understanding the behavior and properties of nanoparticles, aiming at implementing nanotechnology, controlling their behavior and designing new nanomaterials systems with super performance. The book focuses on structural and property characterization of nanocrystals and their assemblies, with an emphasis on basic physical approach, detailed techniques, data interpretation and applications. Intended as a comprehensive reference work for postgraduate students and researchers in the field who are specialized in materials chemistry, materials physics, and materials science.     

Nanotechnology in the Chemical Industry – Opportunities and Challenges

The traditional chemical industry has become a largely mature industry with many commodity products based on established technologies. Therefore, new product and market opportunities will more likely come from speciality chemicals, and from new functionalities obtained from new processing technologies as well as new microstructure control methodologies. It is a well-known fact that in addition to its molecular structure, the microstructure of a material is key to determining its properties. Controlling structures at the micro- and nano-levels is therefore essential to new discoveries. For this article, we define nanotechnology as the controlled manipulation of nanomaterials with at least one dimension less than 100nm. Nanotechnology is emerging as one of the principal areas of investigation that is integrating chemistry and materials science, and in some cases integrating these with biology to create new and yet undiscovered properties that can be exploited to gain new market opportunities. In this article market opportunities for nanotechnology will be presented from an industrial perspective covering electronic, biomedical, performance materials, and consumer products. Manufacturing technology challenges will be identified, including operations ranging from particle formation, coating, dispersion, to characterization, modeling, and simulation. Finally, a nanotechnology innovation roadmap is proposed wherein the interplay between the development of nanoscale building blocks, product design, process design, and value chain integration is identified. A suggestion is made for an R&D model combining market pull and technology push as a way to quickly exploit the advantages in nanotechnology and translate these into customer benefits.     

Dynamic mechanism for encapsulating two HIV replication inhibitor peptides with carbon nanotubes

Encapsulation of biomolecules inside a carbon nanotube(CNT) has attracted great interest because it could enable the delivery of nanoscale pharmaceutical drugs with CNT-based devices.Using a molecular dynamics simulation,we investigate the dynamic process by which human immunodeficiency virus(HIV) replication inhibitor peptides(HRIPs) are encapsulated in a water solution contained inside a CNT.The van der Waals attraction between the HRIPs and the CNT and the root-mean-square deviation are used to analyse the evolution of the encapsulation.It is found that the interaction between the HRIPs and the CNT is the main driving force for the encapsulation process,which does not cause an obvious conformational change to the HRIPs.     

Longitudinal Nanotechnology Development (1991--2002): National Science Foundation Funding and its Impact on Patents

Nanotechnology holds the promise to revolutionize a wide range of products, processes and applications. It is recognized by over sixty countries as critical for their development at the beginning of the 21st century. A significant public investment of over $1 billion annually is devoted to nanotechnology research in the United States. This paper provides an analysis of the National Science Foundation (NSF) funding of nanoscale science and engineering (NSE) and its relationship to the innovation as reflected in the United States Patent and Trade Office (USPTO) patent data. Using a combination of bibliometric analysis and visualization tools, we have identified several general trends, the key players, and the evolution of technology topics in the NSF funding and commercial patenting activities. This study documents the rapid growth of innovation in the field of nanotechnology and its correlation to funding. Statistical analysis shows that the NSF-funded researchers and their patents have higher impact factors than other private and publicly funded reference groups. This suggests the importance of fundamental research on nanotechnology development. The number of cites per NSF-funded inventor is about 10 as compared to 2 for all inventors of NSE-related patents recorded at USPTO, and the corresponding Authority Score is 20 as compared to 1.8.