An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-bioeng-071811-150124

The effect of nanoparticle size, shape, and surface chemistry on biological systems.

The search for understanding the interactions of nanosized materials with living organisms is leading to the rapid development of key applications, including improved drug delivery by targeting nanoparticles, and resolution of the potential threat of nanotechnological devices to organisms and the environment. Unless they are specifically designed to avoid it, nanoparticles in contact with biological fluids are rapidly covered by a selected group of biomolecules to form a corona that interacts with biological systems. Here we review the basic concept of the nanoparticle corona and its structure and composition, and highlight how the properties of the corona may be linked to its biological impacts. We conclude with a critical assessment of the key problems that need to be resolved in the near future.

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Biomolecular coronas provide the biological identity of nanosized materials

Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.

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The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles.

http://pharmaquest.weebly.com/uploads/9/9/4/2/9942916/superparamagnetic_iron_oxide_nanoparticles_spions.pdf

Superparamagnetic iron oxide nanoparticles (SPIONs): Development, surface modification and applications in chemotherapy

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

In the recent decade, the fabrication of nanoparticles and exploration of their properties have attracted the attention of all branches of science such as physicists, chemists, biologists, engineers, and even medical doctors. Interests for nanoparticles arise from the fact that their mechanical, chemical, electrical, optical, magnetic, electro-optical, and magneto-optical properties of these nanoparticles are completely different from their bulk properties and the predetermined differences are depended on the physicochemical properties of the nanoparticles. There are numerous areas where nanoparticles are of scientific and technological interest, specifically for medical community, where the synthetic and biologic worlds come together and lead to an important concern for design of safe nano-biomaterials. In this chapter, we review and discuss the major biomedical applications of nanoparticles. 1.1 Nanoscience in Medicine Nanomedicine is the application of nanosciences to health and exploits the physical, chemical, and biological properties of nanomaterials. The advent of nanoscience and nanotechnologies is shaping the face of industrial production and economics. As a matter of fact, nano-based products now include electronic components, paint, sports equipment, fabrics, sunscreens, and other cosmetics [1]. However, the most exciting nano-innovations reside in the conception of new medical products such as heart valves, drug-delivery systems, and imaging techniques [1], which will surely obliterate the long-established boundaries amidst chemistry, physics, and biology. It is anticipated that nanotechnology will have substantial economic impacts by encouraging productivity and competitiveness, converging different disciplines of science and technologies, and stimulating education and human development [2]. Experts predict market growth to hundreds of billions of dollars in the next decade. The worldwide market for products exploiting nanotechnology reached M. Rahman et al., Protein-Nanoparticle Interactions, Springer Series in Biophysics 15, DOI 10.1007/978-3-642-37555-2_1, © Springer-Verlag Berlin Heidelberg 2013 1 about US$254 billion in 2009, with nanomedical products accounting for a margin of US$72.8 billion in 2011 [3]. The US government has granted more than US$20 billion to the US National Nanotechnology Initiative for nanotechnology research and development activities, facilities, and workforce training since 2000 [4]. In 2011, the Canadian Institutes of Health Research (CIHR) and the Canadian Space Agency (CSA) have granted US $16 million in funding to seven new research projects on regenerative medicine and nanomedicine [5]. The European Framework Program [6] will invest about 600 million euros per year for nanotechnology research until 2013, with a supplementary, comparable sum provided by individual countries [7]. The economic landscape is thus being dramatically altered by nanotechnology. For instance, in 2004, worldwide corporations spent US$3.8 billion on research and development [8]. More importantly, there is a shift from the discovery stage to applications on nanotechnology, as demonstrated by the ratio increased corporate patent applications to scientific publications from 0.23 in 1999 to 1.2 in 2008 [2]. Additionally, analysts estimate that by 2014, nanotechnology will be responsible for 15 % of all manufactured merchandise, valuing approximately US$2.6 trillion and will create 10 million jobs globally [1]. Physicochemical properties of nanoparticles such as their small size, large surface area, and kinetics of adsorption make them particularly interesting as tools for molecular diagnostics, in vivo imaging, and improved treatment of disease. Metal oxides have been introduced in the early 1960s as ferromagnetic separation moieties and have brought about the use of nanoparticles for magnetic resonance imaging (MRI) in the late 1970s. More recently, application of nanoparticles to medicine has expanded to cellular therapy [9], tissue repair [10], drug delivery [11], hyperthermia [12], (MRI) [13], magnetic resonance spectroscopy [14], magnetic separation [15], and as sensors for metabolites and other biomolecule [16]. Moreover, the unique magnetic properties and small size of magnetic nanoparticles (MNPs) make them appealing for biomolecule labeling in bioassays, as well as MRI contrast agents [17]. Superparamagnetic iron oxide (SPIO) can also be used as magnetic gradients for cell sorting in bioreactors [18], as well as absorbing material in radio-frequency hyperthermia. Moreover, the exceptional physical, mechanical, and electronic properties of carbon nanotubes (CNTs) allow them to be used as biosensors, probes, actuators, nanoelectronic devices, drug-delivery systems, and tissue-repair scaffolds within biomedical applications [19–21]. Recent research has focused on conjugating nanocarriers to specific ligands such as peptides, antibodies, and small molecules and subsequently directing them to sites of interest [22]. These techniques can prove to be appealing alternatives for current cancer and cardiovascular applications. Thus, a vast array of nanotechnologies can be applied to medical devices, materials, and processes that will affect the prevention, early diagnosis, and treatment of diseases. However, the risk–benefit balance for these materials, with regard to their toxicological profile and any potential adverse pathogenic reactions from exposure, will ultimately define their clinical outcome. 2 1 The Biological Significance of “Nano”-interactions

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Protein-Nanoparticle Interactions

Surface plasmon resonance detection of E. coli and methicillin-resistant S. aureus using bacteriophages.

Nanoparticles and other nanomaterials are increasingly considered for use in biomedical applications such as imaging, drug delivery, and hyperthermic therapies. Thus, understanding the interaction of nanomaterials with biological systems becomes key for their safe and efficient application. It is increasingly being accepted that the surface of nanomaterials would be covered by protein corona upon their entrance to the biological medium. The biological medium will then see the achieved modified surface of nanomaterials, and therefore further cellular/tissue responses depend on the composition of corona. In this chapter, we describe the corona variations according to the physicochemical properties of nanomaterials (e.g., size, shape, surface charge, surface functional groups, and hydrophilicity/hydrophobicity). Besides the nanomaterials’ effects, the role of environment factors, such as protein source and slight temperature variations, is discussed in details.

Nanoparticle and Protein Corona

Pathogen detection is of utmost importance in many sectors, such as in the food industry, environmental quality control, clinical diagnostics, bio-defence and counter-terrorism. Failure to appropriately, and specifically, detect pathogenic bacteria can lead to serious consequences, and may ultimately be lethal. Public safety, new legislation, recent outbreaks in food contamination, and the ever-increasing prevalence of multidrug-resistant infections have fostered a worldwide research effort targeting novel biosensing strategies. This review concerns phage-based analytical and biosensing methods targeted towards theranostic applications. We discuss and review phage-based assays, notably phage amplification, reporter phage, phage lysis, and bioluminescence assays for the detection of bacterial species, as well as phage-based biosensors, including optical (comprising SPR sensors and fiber optic assays), electrochemical (comprising amperometric, potentiometric, and impedimetric sensors), acoustic wave and magnetoelastic sensors.

Bacteriophages: biosensing tools for multi-drug resistant pathogens

We report the synthesis and characterization of gold–bacteriophage hybrids for biodetection purposes. The physical and optical properties of gold nanoparticles (AuNPs) and the biological features of the phages offer a multifunctional scaffold with great potential for nanotechnologically based biomedical applications. AuNPs, stabilized (PEGylated) using heterobifunctional polyethylene glycol (PEG), were coupled to methicillin-resistant S. aureus-specific phages. The PEG ligands contain a thiol group for stable anchoring to the gold surface and a terminal carboxylic acid group for further coupling to the outside of the PEG shell by carbodiimide chemistry. Transmission electron microscopic analysis showed that the NP–phage bioconjugates are highly stable, with a median diameter of 90 nm. X-ray photoelectron spectroscopy was used to chemically characterize the surfaces of the PEG-functionalized AuNPs, the bacteriophages, and the gold–phage hybrids. The role of the interface and the covalent coupling chemistry...

X‑ray Photoelectron Spectroscopic and Transmission Electron Microscopic Characterizations of Bacteriophage−Nanoparticle Complexes for Pathogen Detection

Nancy Tawil

Papers

Protein-Nanoparticle Interactions

Surface plasmon resonance detection of E. coli and methicillin-resistant S. aureus using bacteriophages.

Nanoparticle and Protein Corona

Bacteriophages: biosensing tools for multi-drug resistant pathogens

X‑ray Photoelectron Spectroscopic and Transmission Electron Microscopic Characterizations of Bacteriophage−Nanoparticle Complexes for Pathogen Detection