RESUMEN
The human iron storage protein ferritin represents an appealing template to obtain a semisynthetic magnetic nanoparticle (MNP) for spatial manipulation or inductive heating applications on a nanoscale. Ferritin consists of a protein cage of well-defined size (12 nm), which is genetically modifiable and biocompatible, and into which a magnetic core is synthesised. Here, we probed the magnetic response and hence the MNP's suitability for (bio-)nanotechnological or nanomedical applications when the core is doped with 7% cobalt or 7% zinc in comparison with the undoped iron oxide MNP. The samples exhibit almost identical core and hydrodynamic sizes, along with their tunable magnetic core characteristics as verified by structural and magnetic characterisation. Cobalt doping significantly increased the MNP's anisotropy and hence the heating power in comparison with other magnetic cores with potential application as a mild heat mediator. Spatial magnetic manipulation was performed with MNPs inside droplets, the cell cytoplasm, or the cell nucleus, where the MNP surface conjugation with mEGFP and poly(ethylene glycol) gave rise to excellent intracellular stability and traceability within the complex biological environment. A magnetic stimulus (smaller than fN forces) results in the quick and reversible redistribution of the MNPs. The obtained data suggest that semisynthetic ferritin MNPs are highly versatile nanoagents and promising candidates for theranostic or (bio-)nanotechnological applications.
Asunto(s)
Cobalto , Ferritinas , Nanopartículas de Magnetita , Ferritinas/química , Humanos , Cobalto/química , Nanopartículas de Magnetita/química , Anisotropía , Calor , Zinc/química , Campos Magnéticos , CalefacciónRESUMEN
Lipopolysaccharide (LPS), also referred to as endotoxin, is the major component of Gram-negative bacteria's outer cell wall. It is one of the main types of pathogen-associated molecular patterns (PAMPs) that are known to elicit severe immune reactions in the event of a pathogen trespassing the epithelial barrier and reaching the bloodstream. Associated symptoms include fever and septic shock, which in severe cases, might even lead to death. Thus, the detection of LPS in medical devices and injectable pharmaceuticals is of utmost importance. However, the term LPS does not describe one single molecule but a diverse class of molecules sharing one common feature: their characteristic chemical structure. Each bacterial species has its own pool of LPS molecules varying in their chemical composition and enabling the aggregation into different supramolecular structures upon release from the bacterial cell wall. As this heterogeneity has consequences for bioassays, we aim to examine the great variability of LPS molecules and their potential to form various supramolecular structures. Furthermore, we describe current LPS quantification methods and the LPS-dependent inflammatory pathway and show how LPS heterogeneity can affect them. With the intent of overcoming these challenges and moving towards a universal approach for targeting LPS, we review current studies concerning LPS-specific binders. Finally, we give perspectives for LPS research and the use of LPS-binding molecules.
Asunto(s)
Lipopolisacáridos , Choque Séptico , Humanos , Endotoxinas , Transducción de Señal , BioensayoRESUMEN
Magnetic nanoparticles (MNPs) are widely known as valuable agents for biomedical applications. Recently, MNPs were further suggested to be used for a remote and non-invasive manipulation, where their spatial redistribution or force response in a magnetic field provides a fine-tunable stimulus to a cell. Here, we investigated the properties of two different MNPs and assessed their suitability for spatio-mechanical manipulations: semisynthetic magnetoferritin nanoparticles and fully synthetic 'nanoflower'-shaped iron oxide nanoparticles. As well as confirming their monodispersity in terms of structure, surface potential, and magnetic response, we monitored the MNP performance in a living cell environment using fluorescence microscopy and asserted their biocompatibility. We then demonstrated facilitated spatial redistribution of magnetoferritin compared to 'nanoflower'-NPs after microinjection, and a higher magnetic force response of these NPs compared to magnetoferritin inside a cell. Our remote manipulation assays present these tailored magnetic materials as suitable agents for applications in magnetogenetics, biomedicine, or nanomaterial research.