There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Rapid growth in nanotechnology is increasing the likelihood of engineered nanomaterials coming into contact with humans and the environment. Nanoparticles interacting with proteins, membranes, cells, DNA and organelles establish a series of nanoparticle/biological interfaces that depend on colloidal forces as well as dynamic biophysicochemical interactions. These interactions lead to the formation of protein coronas, particle wrapping, intracellular uptake and biocatalytic processes that could have biocompatible or bioadverse outcomes. For their part, the biomolecules may induce phase transformations, free energy releases, restructuring and dissolution at the nanomaterial surface. Probing these various interfaces allows the development of predictive relationships between structure and activity that are determined by nanomaterial properties such as size, shape, surface chemistry, roughness and surface coatings. This knowledge is important from the perspective of safe use of nanomaterials.

Understanding biophysicochemical interactions at the nano–bio interface

The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a new paradigm in cancer therapy stem from the complexities and heterogeneity of tumour biology, an incomplete understanding of nano-bio interactions and the challenges regarding chemistry, manufacturing and controls required for clinical translation and commercialization. This Review highlights the progress, challenges and opportunities in cancer nanomedicine and discusses novel engineering approaches that capitalize on our growing understanding of tumour biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

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Cancer nanomedicine: progress, challenges and opportunities.

This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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Analysis of nanoparticle delivery to tumours

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

Temperature-dependent structure and function of group A streptococcal M proteins.This thesis describes the temperature-dependent structure of the members in the group A streptococcal M protein family. M proteins are cell-surface proteins that are important for the bacterial virulence and bind to a diverse set of human plasma proteins. The proteins are dimeric coiled-coil molecules, but temperature unstable, i.e. at 37°C the isolated proteins are monomeric molecules and to a great extent unfolded. It was shown that the Ig-binding by group A streptococcal strains was weaker at 37°C than 20°C. The Ig-binding by isolated M proteins and M-like proteins was, likewise, weaker at 37°C than 20°C. In contrast, the fibrinogen-binding by bacteria was equally strong at 20°C and 37°C, while the fibrinogen-binding by isolated protein was temperature-dependent. The M protein can be divided into class A and C proteins depending on whether centrally located repeats are A- or C-repeats. The coiled-coil structure of a fibrinogen-binding class A protein, Mrp4, was found to be temperature stable with strong fibrinogen-binding also at 37°C. The class A proteins have a higher percentage of hydrophobic amino acids in residues constituting the hydrophobic core in coiled-coil proteins than class C proteins. This disparity was suggested to explain the different temperature stabilities in class A and C proteins. The temperature stability also varies among class C proteins and higher temperature stability is accompanied by higher percentage hydrophobic amino acids in the hydrophobic core. The unfolding of M proteins indicated one to three structural regions. Furthermore, near-UV circular dichroism studies indicated a lower temperature stability of the N-terminal half of protein H, a class C proteins, compared to the overall helical structure. In opposite, the binding of IgG by protein H stabilised the N-terminal half to a higher extent than the overall helical structure.

Temperature-dependent structure and function of group A streptococcal M proteins

Micro- and nanoplastic pollution has emerged as a global environmental problem. Moreover, plastic particles are of increasing concern for human health. However, the detection of so-called nanoplastics in relevant biological compartments remains a challenge. Here we show that Raman confocal spectroscopy-microscopy can be deployed for the non-invasive detection of amine-functionalized and carboxy-functionalized polystyrene (PS) nanoparticles (NPs) in Daphnia magna. The presence of PS NPs in the gastrointestinal (GI) tract of D. magna was confirmed by using transmission electron microscopy. Furthermore, we investigated the ability of NH2-PS NPs and COOH-PS NPs to disrupt the epithelial barrier of the GI tract using the human colon adenocarcinoma cell line HT-29. To this end, the cells were differentiated for 21 days and then exposed to PS NPs followed by cytotoxicity assessment and transepithelial electrical resistance measurements. A minor disruption of barrier integrity was noted for COOH-PS NPs, but not for the NH2-PS NPs, while no overt cytotoxicity was observed for both NPs. This study provides evidence of the feasibility of applying label-free approaches, i.e., confocal Raman mapping, to study PS NPs in a biological system.

Label-free detection of polystyrene nanoparticles in Daphnia magna using Raman confocal mapping

Abstract The attention to rare earth oxide nanoparticles (NPs), including yttrium oxide (Y2O3), has increased in many fields due to their unique structural characteristics and functional properties. The aim of our study was to investigate the mechanisms by which bio-corona formation on Y2O3 NPs affects their environmental fate and toxicity. The Y2O3 NPs induced toxicity to freshwater filter feeder Daphnia magna at particle concentrations of 1 and 10 mg/L, regardless of particle size. Interactions between naturally excreted biomolecules (e.g. protein, lipids, and polysaccharides) derived from D. magna, and the Y2O3 NPs (30–45 nm) resulted in the formation of an eco-corona, which reduced their toxic effects toward D. magna at a particle concentration of 10 mg/L. No effects were observed at lower concentrations or for the other particle sizes investigated. Copper-zinc (Cu-Zn) superoxide dismutase, apolipophorins, and vitellogenin-1 proteins proved to be the most prominent proteins of the adsorbed corona, and possibly a reason for the reduced toxicity of the 30–45 nm Y2O3 NPs toward D. magna.

https://www.tandfonline.com/doi/pdf/10.1080/17435390.2023.2226712?needAccess=true&role=button

The effect of natural biomolecules on yttrium oxide nanoparticles from a Daphnia magna survival rate perspective

Nanoplastics are defined as plastic particles broken down to extremely small sizes (1–100 nm) with unknown effects to the human body and immune system. Air and food exposure scenarios involving blood, lungs and intestine are considered in the literature. The fact that plastics also needs to pass the nose, oral cavity, and throat is so far ignored in the literature. The tonsils are immunologically important tissue in the oral cavity in which ingested and inhaled agents are incorporated through crypts with the capacity to capture agents and start early immunologic reactions. We argue that the tonsil is a very important tissue to study in regard to micro and nanoplastic human exposure and immunologic response. Nano-sized particles are known to be able to travel through the natural barriers and have different effects on biology compared to larger particle and the bulk material. It is therefore, although difficult, important to develop experimental methods to detect and identify nanoplastics in the tonsils. In preliminary experiments we have optimized the breakdown of tonsil tissues and tried to retrieve added polystyrene nanoparticles using density-based separation and concentration. The polystyrene was followed by FTIR spectrometry and could be detected in micro- and nano-size, in the tissue breakdown solution but not after density-based separation. When nanoplastics are incorporated in the human body, it is possible that the small plastic pieces can be detected in the tonsil tissue, in the lymph system and it is of importance for future studies to reveal the immunological effects for humans.

The forgotten tonsils—does the immune active organ absorb nanoplastics?

Particles used in the study: 53 nm PS-NH 2 and 62 nm PS-COOH. Significant metabolic responses at: 3.2 μg L −1 PS NPs. 

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Tommy Cedervall

Papers

Temperature-dependent structure and function of group A streptococcal M proteins

Label-free detection of polystyrene nanoparticles in Daphnia magna using Raman confocal mapping

The effect of natural biomolecules on yttrium oxide nanoparticles from a Daphnia magna survival rate perspective

The forgotten tonsils—does the immune active organ absorb nanoplastics?

Metabolomics-based analysis in <i>Daphnia magna</i> after exposure to low environmental concentrations of polystyrene nanoparticles