Force-Mediated Endocytosis of Iron Oxide Nanoparticles for Magnetic Targeting of Stem Cells

Abstract

Stem cell therapy represents one of the most promising approaches for tissue repair and regeneration. However, the full potential of stem cell therapy remains to be realized. One major challenge is the insufficient homing and retention of stem cells at the desired sites after in vivo delivery. Here, we provide a proof-of-principle demonstration of magnetic targeting and retention of human muscle-derived stem cells (hMDSCs) in vitro through magnetic force-mediated internalization of magnetic iron oxide nanoparticles (MIONs) and the use of a micropatterned magnet. We found that the magnetic force-mediated cellular uptake of MIONs occurs through an endocytic pathway, and the MIONs were exclusively localized in the lysosomes. The intracellular MIONs had no detrimental effect on the proliferation of hMDSCs or their multilineage differentiation, and no MIONs were translocated to other cells in a coculture system. Using hMDSCs and three other cell types including human umbilical vein endothelial cells (HUVECs), human dermal fibroblasts (HDFs), and HeLa cells, we further discovered that the magnetic force-mediated MION uptake increased with MION size and decreased with cell membrane tension. We found that the cellular uptake rate was initially increased with MION concentration in solution and approached saturation. These findings provide important insight and guidance for magnetic targeting of stem cells in therapeutic applications.

Application of Nanoparticles for Magnetic Hyperthermia for Cancer Treatment—The Current State of Knowledge

“…Biocompatibility studies with human umbilical vein endothelial cells (HUVECs) showed that endocytosis is the main mechanism of the intracellular transport of dextran- and citric acid-coated SPIONs. Additionally, SPIONs were found to inhibit the migration and induce apoptosis of HUVECs [ 60 ]. An in vivo animal study revealed that the pharmacokinetics and biodistribution of MNPs were dependent on the mode of administration, hydrodynamic diameter, and surface charge.…”

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

“…In addition, SPION can be used for drug delivery and magnetic thermotherapy. In drug delivery, drugs can be encapsulated in NPs and delivered precisely to the lesion site by magnetic field induction, thereby improving drug efficacy and reducing side effects 147–149 . As for magnetic hyperthermia, the heat generated by NPs in an alternating magnetic field (AMF) can be used to kill tumor cells, thus achieving the goal of treating tumors 150–152 .…”

“…In drug delivery, drugs can be encapsulated in NPs and delivered precisely to the lesion site by magnetic field induction, thereby improving drug efficacy and reducing side effects. 147 , 148 , 149 As for magnetic hyperthermia, the heat generated by NPs in an alternating magnetic field (AMF) can be used to kill tumor cells, thus achieving the goal of treating tumors. 150 , 151 , 152 In conclusion, SPION is a promising nanomaterial with a wide range of applications, and research on its preparation and application is constantly deepening and developing.…”

Iron oxide nanozymes enhanced by ascorbic acid for macrophage-based cancer therapy

“…Previous studies have established that nanoparticles encapsulated in phospholipid-PEG coating are internalized by cells through endocytic pathways, accumulating in endosomes and lysosomes with pH levels ranging from 4 to 5. 39 Taken together, when only intracellular WNPs are present, ascorbic acid can generate H 2 O 2 in the medium, which then permeates cells and encounters WNPs accumulated in the acidic cell organelles. Under optimal pH conditions, WNPs efficiently convert H 2 O 2 into toxic hydroxyl free radicals.…”