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 (Ca 2+ ) 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, NaGdF 4 @PDA‐ALD nanoparticles (NPANs) are synthesized, featuring a NaGdF 4 core coated with polydopamine (PDA) for ROS scavenging and further modified with alendronate sodium (ALD) for Ca 2+ chelation. The internalization of NPANs by MSCs protected them from oxidative damage and calcium overload, thereby promoting their viability and functionality. Furthermore, NaGdF 4 generated T 1 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.