'Stealth' nanoparticles evade neural immune cells but also evade major brain cell populations: Implications for PEG-based neurotherapeutics

Surface engineering to control cell behavior is of high interest across the chemical engineering, drug delivery and biomaterial communities. Defined chemical strategies are necessary to tailor nanoscale protein interactions/adsorption, enabling control of cell behaviors for development of novel therapeutic strategies. Nanoparticle-based therapies benefit from such strategies but particle targeting to sites of neurological injury remains challenging due to circulatory immune clearance. As a strategy to overcome this barrier, the use of stealth coatings can reduce immune clearance and prolong circulatory times, thereby enhancing therapeutic capacity. Polyethylene glycol (PEG) is the most widely-used stealth coating and facilitates particle accumulation in the brain. However, once within the brain, the mode of handling of PEGylated particles by the resident immune cells of the brain itself (the ‘microglia’) is unknown. This is a critical question as it is well established that microglia avidly sequester nanoparticles, limiting their bioavailability and posing a major translational barrier. If PEGylation can be proved to promote evasion of microglia, then this information will be of high value in developing tailored nanoparticle-based therapies for neurological applications. Here, we have conducted the first comparative study of uptake of PEGylated particles by all the major (immune and non-immune) brain cell types. We prove for the first time that PEGylated nanoparticles evade major brain cell populations — a phenomenon which will enhance extracellular bioavailability. We demonstrate changes in protein coronas around these particles within biological media, and discuss how surface chemistry presentation may affect this process and subsequent cellular interactions

Microbial Reduction of Arsenic-Doped Schwertmannite by <i>Geobacter sulfurreducens</i>

The fate of As­(V) during microbial reduction by <i>Geobacter sulfurreducens</i> of Fe­(III) in synthetic arsenic-bearing schwertmannites has been investigated. During incubation at pH7, the rate of biological Fe­(III) reduction increased with increasing initial arsenic concentration. From schwertmannites with a relatively low arsenic content (<0.3 wt %), only magnetite was formed as a result of dissimilatory iron reduction. However, bioreduction of schwertmannites with higher initial arsenic concentrations (>0.79 wt %) resulted in the formation of goethite. At no stage during the bioreduction process did the concentration of arsenic in solution exceed 120 μgL¹, even for a schwertmannite with an initial arsenic content of 4.13 wt %. This suggests that the majority of the arsenic is retained in the biominerals or by sorption at the surfaces of newly formed nanoparticles.Subtle differences in the As <i>K</i>-edge XANES spectra obtained from biotransformation products are clearly related to the initial arsenic content of the schwertmannite starting materials. For products obtained from schwertmannites with higher initial As concentrations, one dominant population of As­(V) species bonded to only two Fe atoms was evident. By contrast, schwertmannites with relatively low arsenic concentrations gave biotransformation products in which two distinctly different populations of As­(V) persisted. The first is the dominant population described above, the second is a minority population characterized by As­(V) bonded to four Fe atoms. Both XAS and XMCD evidence suggest that the latter form of arsenic is that taken into the tetrahedral sites of the magnetite.We conclude that the majority population of As­(V) is sorbed to the surface of the biotransformation products, whereas the minority population comprises As­(V) incorporated into the tetrahedral sites of the biomagnetite. This suggests that microbial reduction of highly bioavailable As­(V)-bearing Fe­(III) mineral does not necessarily result in the mobilization of the arsenic