Dual Ion Releasing Nanoparticles for Modulating Osteogenic Cellular Microenvironment of Human Mesenchymal Stem Cells

Abstract

In this study we developed a dual therapeutic metal ion-releasing nanoparticle for advanced osteogenic differentiation of stem cells. In order to enhance the osteogenic differentiation of human mesenchymal stem cells (hMSCs) and induce angiogenesis, zinc (Zn) and iron (Fe) were synthesized together into a nanoparticle with a pH-sensitive degradation property. Zn and Fe were loaded within the nanoparticles to promote early osteogenic gene expression and to induce angiogenic paracrine factor secretion for hMSCs. In vitro studies revealed that treating an optimized concentration of our zinc-based iron oxide nanoparticles to hMSCs delivered Zn and Fe ion in a controlled release manner and supported osteogenic gene expression (RUNX2 and alkaline phosphatase) with improved vascular endothelial growth factor secretion. Simultaneous intracellular release of Zn and Fe ions through the endocytosis of the nanoparticles further modulated the mild reactive oxygen species generation level in hMSCs without cytotoxicity and thus improved the osteogenic capacity of the stem cells. Current results suggest that our dual ion releasing nanoparticles might provide a promising platform for future biomedical applications.

Extracellular Vesicle Mimetics: Preparation from Top‐Down Approaches and Biological Functions

“…[ 32b ] The internalization process can also be monitored via fluorescence microscopy after staining EVMs with the fluorescent stain, DiO. [ 80 ] The mechanisms underlying EVMs uptake remain unclear. In general, naturally isolated EVs are internalized by target cells through direct fusion with the plasma membrane and endocytosis, via various pathways, such as clathrin‐dependent endocytosis, caveolin‐mediated uptake, macropinocytosis, phagocytosis, and lipid raft‐mediated internalization.…”