Increasing the Efficacy of Stem Cell Therapy via Triple-Function Inorganic Nanoparticles

• Published in: ACS nano Vol. 13; no. 6; pp. 6605 - 6617
• Main Authors: Chen, Fang, Zhao, Eric Ruike, Hableel, Ghanim, Hu, Tao, Kim, Taeho, Li, Jingting, Gonzalez-Pech, Natalia Isabel, Cheng, David J, Lemaster, Jeanne E, Xie, Yijun, Grassian, Vicki H, Sen, George L, Jokerst, Jesse V
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25.06.2019
• Subjects: Animals; Cells, Cultured; Contrast Media - chemistry; Drug Liberation; Ferric Compounds - chemistry; Humans; Insulin-Like Growth Factor I - administration & dosage; Insulin-Like Growth Factor I - pharmacology; Magnetic Resonance Imaging - methods; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells - drug effects; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; Myocardial Infarction - diagnostic imaging; Myocardial Infarction - therapy; Nanoparticles - chemistry; Silicon Dioxide - chemistry; Theranostic Nanomedicine - methods; theranostic nanoparticles; cell manipulation; contrast agents; stem cell therapy; mesoporous silica−iron oxide nanoparticles
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.9b00653

Stem cell therapy in heart disease is challenged by mis-injection, poor survival, and low cell retention. Here, we describe a biocompatible multifunctional silica–iron oxide nanoparticle to help solve these issues. The nanoparticles were made via an in situ growth of Fe3O4 nanoparticles on both the external surfaces and pore walls of mesocellular foam silica nanoparticles. In contrast to previous work, this approach builds a magnetic moiety inside the pores of a porous silica structure. These materials serve three roles: drug delivery, magnetic manipulation, and imaging. The addition of Fe3O4 to the silica nanoparticles increased their colloidal stability, T 2-based magnetic resonance imaging contrast, and superparamagnetism. We then used the hybrid materials as a sustained release vehicle of insulin-like growth factora pro-survival agent that can increase cell viability. In vivo rodent studies show that labeling stem cells with this nanoparticle increased the efficacy of stem cell therapy in a ligation/reperfusion model. The nanoparticle-labeled cells increase the mean left ventricular ejection fraction by 11 and 21% and the global longitudinal strain by 24 and 34% on days 30 and 60, respectively. In summary, this multifunctional nanomedicine improves stem cell survival via the sustained release of pro-survival agents.