Stem cell therapy
in heart disease is challenged by mis-injection,
poor survival, and low cell retention. Here, we describe a biocompatible
multifunctional silica–iron oxide nanoparticle to help solve
these issues. The nanoparticles were made via an in situ growth of Fe3O4 nanoparticles
on both the external surfaces and pore walls of mesocellular foam
silica nanoparticles. In contrast to previous work, this approach
builds a magnetic moiety inside the pores of a porous silica structure.
These materials serve three roles: drug delivery, magnetic manipulation,
and imaging. The addition of Fe3O4 to the silica
nanoparticles increased their colloidal stability, T
2-based magnetic resonance imaging contrast, and superparamagnetism.
We then used the hybrid materials as a sustained release vehicle of
insulin-like growth factora pro-survival agent that can increase
cell viability. In vivo rodent studies show that
labeling stem cells with this nanoparticle increased the efficacy
of stem cell therapy in a ligation/reperfusion model. The nanoparticle-labeled
cells increase the mean left ventricular ejection fraction by 11 and
21% and the global longitudinal strain by 24 and 34% on days 30 and
60, respectively. In summary, this multifunctional nanomedicine improves
stem cell survival via the sustained release of pro-survival
agents.
Exposures to high doses of manganese (Mn) via inhalation, dermal contact or direct consumption can cause adverse health effects. Welding fumes are a major source of manganese containing nanoparticles in occupational settings. Understanding the physicochemical properties of manganese-containing nanoparticles can be a first step in understanding their toxic potential following exposure. In particular, here we compare the size, morphology and Mn oxidation states of Mn oxide nanoparticles generated in the laboratory by arc discharge to those from welding collected in heavy vehicle manufacturing. Fresh nanoparticles collected at the exit of the spark discharge generation chamber consisted of individual or small aggregates of primary particles. These nanoparticles were allowed to age in a chamber to form chain-like aggregates of primary particles with morphologies very similar to welding fumes. The primary particles were a mixture of hausmannite (Mn3O4), bixbyite (Mn2O3) and manganosite (MnO) phases, whereas aged samples revealed a more amorphous structure. Both Mn2+ and Mn3+, as in double valence stoichiometry present in Mn3O4, and Mn3+, as in Mn2O3 and MnOOH, were detected by X-ray photoelectron spectroscopy on the surface of the nanoparticles in the laboratory nanoparticles and welding fumes. Dissolution studies conducted for these two Mn samples (aged and fresh fume) reveal different release kinetics of Mn ions in artificial lysosomal fluid (pH 4.5) and very limited dissolution in Gamble’s solution (pH 7.4). Taken together, these data suggest several important considerations for understanding the health effects of welding fumes. First, the method of particle generation affects the crystallinity and phase of the oxide. Second, welding fumes consist of multiple oxidation states whether they are amorphous or crystalline or occur as isolated nanoparticles or agglomerates. Third, although the dissolution behavior depends on conditions used for nanoparticle generation, the dissolution of Mn oxide nanoparticles in the lysosome may promote Mn ions translocation into various organs causing toxic effects.
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