Mesenchymal Stem Cells With Polydopamine-Coated NaGdF₄ Nanoparticles with Ca²⁺ Chelation Ability for Ischemic Stroke Therapy.

Abstract

Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for ischemic stroke. However, the survival of transplanted MSCs is often compromised by the excessive levels of reactive oxygen species (ROS) and calcium ions (Ca²⁺) in the ischemic microenvironment following blood flow occlusion. In this study, a protective strategy is developed using functional nanomaterials to escort and shield MSCs. Specifically, NaGdF₄@PDA-ALD nanoparticles (NPANs) are synthesized, featuring a NaGdF₄ core coated with polydopamine (PDA) for ROS scavenging and further modified with alendronate sodium (ALD) for Ca²⁺ chelation. The internalization of NPANs by MSCs protected them from oxidative damage and calcium overload, thereby promoting their viability and functionality. Furthermore, NaGdF₄ generated T₁ signal enhancement, enabling in vivo tracking of MSCs via magnetic resonance imaging. The NPANs-treated MSCs demonstrated improved survival and migration to the ischemic region, promoting blood flow restoration and angiogenesis. These findings confirm the feasibility of employing functional nanoparticles to augment MSCs-based therapies, offering a promising strategy to improve their therapeutic efficacy in ischemic stroke treatment.