Theranostic Mesoporous Silica Nanoparticles Biodegrade after Pro-Survival Drug Delivery and Ultrasound/Magnetic Resonance Imaging of Stem Cells

Paul J. Kempen^1,2*, Sarah Greasley⁴, Kelly A. Parker², Jos L. Campbell^1#, Huan-Yu Chang¹, Julian R. Jones⁴, Robert Sinclair³, Sanjiv S. Gambhir^1,2,3, Jesse V. Jokerst^1†✉

1. Molecular Imaging Program at Stanford (MIPS), Department of Radiology, 318 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305-5427;
2. Materials Science & Engineering, Stanford University, Stanford, CA 94305;
3. Bioengineering, Bio-X, Stanford University, Stanford, CA 94305;
4. Department of Materials, Imperial College London, Exhibition Road, London, UK SW7 2AZ.
^* New address: Department of Micro- and Nanotechnology, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
^# New address: NanoBiotechnology Research Laboratory (NBRL), School of Applied Sciences, RMIT University, GPO Box 2476 V, Melbourne, VIC 3001, Australia
^† This author's address effective July 2015: Department of NanoEngineering, University of California, San Diego.

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Citation:
Kempen PJ, Greasley S, Parker KA, Campbell JL, Chang HY, Jones JR, Sinclair R, Gambhir SS, Jokerst JV. Theranostic Mesoporous Silica Nanoparticles Biodegrade after Pro-Survival Drug Delivery and Ultrasound/Magnetic Resonance Imaging of Stem Cells. Theranostics 2015; 5(6):631-642. doi:10.7150/thno.11389. Available from http://www.thno.org/v05p0631.htm

Abstract

Increasing cell survival in stem cell therapy is an important challenge for the field of regenerative medicine. Here, we report theranostic mesoporous silica nanoparticles that can increase cell survival through both diagnostic and therapeutic approaches. First, the nanoparticle offers ultrasound and MRI signal to guide implantation into the peri-infarct zone and away from the most necrotic tissue. Second, the nanoparticle serves as a slow release reservoir of insulin-like growth factor (IGF)—a protein shown to increase cell survival. Mesenchymal stem cells labeled with these nanoparticles had detection limits near 9000 cells with no cytotoxicity at the 250 µg/mL concentration required for labeling. We also studied the degradation of the nanoparticles and showed that they clear from cells in approximately 3 weeks. The presence of IGF increased cell survival up to 40% (p<0.05) versus unlabeled cells under in vitro serum-free culture conditions.

Keywords: Stem Cell Therapy, Theranostic, Pro-survival, Mesoporous Silica Nanoparticles.