Biosynthesis of magnetic nanoparticles from nano-degradation products revealed in human stem cells

Abstract

While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells’ differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Using magnetism as a fingerprint of the transformation process, we evidenced an important degradation of the nanoparticles during chondrogenesis. For the other pathways, stem cells were remarkably “remagnetized” after degradation of nanoparticles. This remagnetization phenomenon is the direct demonstration of a possible neosynthesis of magnetic nanoparticlesin celluloand could lay some foundation to understand the presence of magnetic crystals in human cells. The neosynthesis was shown to take place within the endosomes and to involve the H-subunit of ferritin. Moreover, it appeared to be the key process to avoid long-term cytotoxicity (impact on differentiation) related to high doses of magnetic nanoparticles within stem cells.

Airborne Magnetite- and Iron-Rich Pollution Nanoparticles: Potential Neurotoxicants and Environmental Risk Factors for Neurodegenerative Disease, Including Alzheimer’s Disease

“…Over timescales of days, the dosed maghemite NPs were internalised and first dissolved within the cells. Subsequently, magnetite/maghemite NPs were re-formed (via the H sub-unit of ferritin), as abundant, rounded, ~8-nm particles [54]. In this study, the maghemite NPs induced slight inhibition of iron internalization (transferrin expression was down-regulated) and enhanced both iron export (ferroportin expression up-regulated) and…”

Impact of magnetic nanoparticle surface coating on their long-term intracellular biodegradation in stem cells

“…Herein, we studied the cellular uptake and biodegradation of a set of iron oxide nanoparticles formulations that differ only by their coating, using an hMSC spheroid model established as a unique tool to monitor biodegradation. 47,49,50 Starting from the same nanoplatform, we focused on the role played by (i) the coatings chelating function by using different molecules such as citric acid (carboxylic), caffeic acid (catechol) and phosphonoacetic acid (phosphonate), (ii) the number of chelating functions (3 vs 13 carboxylic-groups for citric acid and polyacrylic acid, respectively), (iii) the presence of a PEG spacer between the surface-binding function and the terminal external carboxylic group (-COOH vs -PEG-COOH) and also (iv) the presence of serum proteins. First, we evidenced that the coating has a pivotal impact on the cellular uptake.…”

Challenges in Tracking of Fluorochrome-Labelled Nanoparticles in Mice via Whole Body NIRF Imaging

“…Interestingly, ferritin is capable of caging Fe 3+ under acidic conditions [20], and ferritin-loaded Kupffer cells might favor MNP dye DY-730 fluorescence. On the other hand, neosynthesis of iron oxide nanoparticles from nanodegradation products within the endosomes has been postulated and, interestingly, H-subunits of ferritin may be involved in this process [26]. Under these conditions, one would expect an improved fluorescence-based MNP localization in the liver and spleen.…”