Clustered nanocarriers: the effect of size on the clustering of CCMV virus-like particles with soft macromolecules

Virus-like particles (VLP) could enable a wide variety of biomedical applications in therapy, drug delivery, and imaging. They are biocompatible and can be self-assembled into larger structured materials for additional functionality and potentially better biodistribution, which is still a challenging aspect. Here we investigate the role of the VLPs size and resulting Caspar Klug symmetry in forming clusters out of these building blocks, showing that the onset point for clustering is determined by steric considerations of the binding site and binding agent. The clustering is independent of cargo and the data suggests that rotational symmetry in the T = 3 capsid allows for hexagonal close packed structures, whereas the T = 1 capsid that lacks a six-fold and twofold rotational axis does not show such organization

Viral capsids as templates for the production of monodisperse Prussian blue nanoparticles

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Construction of core-shell hybrid nanoparticles templated by virus-like particles

Plant viruses have been widely used as templates for the synthesis of organic-inorganic hybrids. However, the fine-tuning of hybrid nanoparticle structures, especially the control of inorganic particle size as well as where the silication occurs (i.e. outside and/or inside of the capsid), by simply tuning the pH remains a challenge. By taking advantage of the templating effect of Cowpea Chlorotic Mottle Virus (CCMV) protein cages, we show that the silication at the exterior or interior surface of protein capsids, as well as the resulting structures of silica/virus hybrid nanoparticles can be fine-tuned by pH. At pH 4.0, only small silica particles (diameter of 2.5 nm) were formed inside the protein cages; at pH 6.0, silication mainly takes place inside of the protein cages, leading to monodisperse silica nanoparticles with diameters of 14 nm; and at pH 7.5, silica deposition takes place both at the interior and exterior surfaces of protein cages in aqueous conditions. Under these reaction conditions, multiple component hybrid virus/nanoparticulate systems, such as CCMVAu/silica and Au/silica nanoparticles were prepared step-by-step. Upon removal of the CCMV template by thermal degradation a single gold nanoparticle can be encapsulated in a hollow silica shell emulating the structure of a baby's rattle with an unattached solid particle within a hollow particle. The Au/silica core-hollow shell nanoparticles can then be further used as a stable catalyst. It is anticipated that these synthetic methods provide a versatile methodology to prepare core-shell nanomaterials with well-designed structure and functionality

Early clinical experience with a total body irradiation technique using field-in-field beams and on-line image guidance

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Construction of core-shell hybrid nanoparticles templated by virus-like particles

Plant viruses have been widely used as templates for the synthesis of organic–inorganic hybrids. However, the fine-tuning of hybrid nanoparticle structures, especially the control of inorganic particle size as well as where the silication occurs (i.e. outside and/or inside of the capsid), by simply tuning the pH remains a challenge. By taking advantage of the templating effect of Cowpea Chlorotic Mottle Virus (CCMV) protein cages, we show that the silication at the exterior or interior surface of protein capsids, as well as the resulting structures of silica/virus hybrid nanoparticles can be fine-tuned by pH. At pH 4.0, only small silica particles (diameter of 2.5 nm) were formed inside the protein cages; at pH 6.0, silication mainly takes place inside of the protein cages, leading to monodisperse silica nanoparticles with diameters of 14 nm; and at pH 7.5, silica deposition takes place both at the interior and exterior surfaces of protein cages in aqueous conditions. Under these reaction conditions, multiple component hybrid virus/nanoparticulate systems, such as CCMVAu/silica and Au/silica nanoparticles were prepared step-by-step. Upon removal of the CCMV template by thermal degradation a single gold nanoparticle can be encapsulated in a hollow silica shell emulating the structure of a baby's rattle with an unattached solid particle within a hollow particle. The Au/silica core-hollow shell nanoparticles can then be further used as a stable catalyst. It is anticipated that these synthetic methods provide a versatile methodology to prepare core–shell nanomaterials with well-designed structure and functionality

Pt, Co-Pt and Fe-Pt alloy nanoclusters encapsulated in virus capsids

Nanostructured Pt-based alloys show great promise, not only for catalysis but also in medical and magnetic applications. To extend the properties of this class of materials, we have developed a means of synthesizing Pt and Pt-based alloy nanoclusters in the capsid of a virus. Pure Pt and Pt-alloy nanoclusters are formed through the chemical reduction of [PtCl4]− by NaBH4 with/without additional metal ions (Co or Fe). The opening and closing of the ion channels in the virus capsid were controlled by changing the pH and ionic strength of the solution. The size of the nanoclusters is limited to 18 nm by the internal diameter of the capsid. Their magnetic properties suggest potential applications in hyperthermia for the Co–Pt and Fe–Pt magnetic alloy nanoclusters. This study introduces a new way to fabricate size-restricted nanoclusters using virus capsid

Appetite at "high altitude" [Operation Everest III (Comex-'97)]: a simulated ascent of Mount Everest.

Maastricht University, Maastricht, The Netherlands. [email protected] We hypothesized that progressive loss of body mass during high-altitude sojourns is largely caused by decreased food intake, possibly due to hypobaric hypoxia. Therefore we assessed the effect of long-term hypobaric hypoxia per se on appetite in eight men who were exposed to a 31-day simulated stay at several altitudes up to the peak of Mt. Everest (8,848 m). Palatable food was provided ad libitum, and stresses such as cold exposure and exercise were avoided. At each altitude, body mass, energy, and macronutrient intake were measured; attitude toward eating and appetite profiles during and between meals were assessed by using questionnaires. Body mass reduction of an average of 5 +/- 2 kg was mainly due to a reduction in energy intake of 4.2 +/- 2 MJ/day (P < 0.01). At 5,000- and 6,000-m altitudes, subjects had hardly any acute mountain sickness symptoms and meal size reductions (P < 0.01) were related to a more rapid increase in satiety (P < 0.01). Meal frequency was increased from 4 +/- 1 to 7 +/- 1 eating occasions per day (P < 0. 01). At 7,000 m, when acute mountain sickness symptoms were present, uncoupling between hunger and desire to eat occurred and prevented a food intake necessary to meet energy balance requirements. On recovery, body mass was restored up to 63% after 4 days; this suggests physiological fluid retention with the return to sea level. We conclude that exposure to hypobaric hypoxia per se appears to be associated with a change in the attitude toward eating and with a decreased appetite and food intake

Protein Cages as Containers for Gold Nanoparticles

Abundant and highly diverse, viruses offer new scaffolds in nanotechnology for the encapsulation, organization, or even synthesis of novel materials. In this work the coat protein of the cowpea chlorotic mottle virus (CCMV) is used to encapsulate gold nanoparticles with different sizes and stabilizing ligands yielding stable particles in buffered solutions at neutral pH. The sizes of the virus-like particles correspond to <i>T</i> = 1, 2, and 3 Caspar–Klug icosahedral triangulation numbers. We developed a simple one-step process enabling the encapsulation of commercially available gold nanoparticles without prior modification with up to 97% efficiency. The encapsulation efficiency is further increased using bis-p-(sufonatophenyl)­phenyl phosphine surfactants up to 99%. Our work provides a simplified procedure for the preparation of metallic particles stabilized in CCMV protein cages. The presented results are expected to enable the preparation of a variety of similar virus-based colloids for current focus areas