Superparamagnetic iron oxide nanoparticles (SPIONs) have mainly been used as cellular carriers for genes and therapeutic products, while their use in subcellular organelle isolation remains underexploited. We engineered SPIONs targeting distinct subcellular compartments. Dimercaptosuccinic acid-coated SPIONs are internalized and accumulate in late endosomes/lysosomes, while aminolipid-SPIONs reside at the plasma membrane. These features allowed us to establish standardized magnetic isolation procedures for these membrane compartments with a yield and purity permitting proteomic and lipidomic profiling. We validated our approach by comparing the biomolecular compositions of lysosomes and plasma membranes isolated from wild-type and Niemann-Pick disease type C1 (NPC1) deficient cells. While the accumulation of cholesterol and glycosphingolipids is seen as a primary hallmark of NPC1 deficiency, our lipidomics analysis revealed the buildup of several species of glycerophospholipids and other storage lipids in selectively late endosomes/lysosomes of NPC1-KO cells. While the plasma membrane proteome remained largely invariable, we observed pronounced alterations in several proteins linked to autophagy and lysosomal catabolism reflecting vesicular transport obstruction and defective lysosomal turnover resulting from NPC1 deficiency. Thus the use of SPIONs provides a major advancement in fingerprinting subcellular compartments, with an increased potential to identify disease-related alterations in their biomolecular compositions.

Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

Iron oxide nanoparticles (IONPs) for magnetic hyperthermia in cancer treatment have recently gained substantial interest. Unfortunately, the use of free IONPs still faces major challenges such as poor tumor targetability, high variability in the amount of IONPs taken up by the tumor and the IONP leakage from dead cancer cells into the surrounding healthy tissues. The present work reports on electrospun fiber webs, heavily loaded with 50 nm sized IONPs. The high loading capacity of the fibers enables significant heating of the environment upon applying an alternating magnetic field. Furthermore, magnetic fibers can be repeatedly heated without loss of heating capacity or release of IONPs. Upon functionalization of the fiber surface with collagen, human SKOV‐3 ovarian cancer cells attached well to the fibers. Applying an alternating magnetic field during 10 minutes to the fiber webs killed all fiber‐associated cancer cells. Killing the cells using this method seemed more efficient compared to the use of a warm water bath. As the fiber webs can be i) loaded with a well‐controlled amount of IONPs and ii) localized in the body by Magnetic Resonance Imaging, magnetic electrospun fibers may become promising materials for a highly reproducible (repeated) heating of cancer tissues in vivo.