Stem cell-mediated delivery of nanogels loaded with ultrasmall iron oxide nanoparticles for enhanced tumor MR imaging

Abstract

The development of new nanoplatforms with enhanced tumor accumulation for accurate diagnosis still remains a great challenge in current precision nanomedicine. Herein, we report the design of stem cell-mediated delivery of nanogels (NGs) loaded with ultrasmall iron oxide (Fe₃O₄) nanoparticles (NPs) for enhanced magnetic resonance (MR) imaging of tumors. In this study, sodium citrate-stabilized ultrasmall Fe₃O₄ NPs with a size of 3.16 ± 1.30 nm were first synthesized using a solvothermal route, coated with polyethyleneimine (PEI), and used as crosslinkers to crosslink alginate (AG) NGs formed via a double emulsion approach, where the AG carboxyl groups were pre-activated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride. The thus prepared Fe₃O₄ NP-loaded NGs (AG/PEI-Fe₃O₄ NGs) with a size of 47.68 ± 3.41 nm are water-dispersible, colloidally stable, cytocompatible in a given concentration range, display a relatively high r₁ relaxivity (r₁ = 1.5 mM⁻¹ s⁻¹), and are able to be taken up by bone mesenchymal stem cells without compromising cell viability and stem cell characteristics. Due to the tumor-chemotaxis or tumor tropism, the BMSCs are able to mediate the enhanced delivery of AG/PEI-Fe₃O₄ NGs to the tumor site after intravenous injection, thus enabling significantly strengthened MR imaging of tumors when compared to free NGs. These findings suggest that the developed AG/PEI-Fe₃O₄NGs, once mediated by stem cells may serve as a novel, safe, effective and targeted platform for enhanced MR imaging of tumors.