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Characterization of Superparamagnetic Nanoparticle Interactions with Extracellular Matrix in an in Vitro System

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Abstract

Controlled dispersion of therapeutic agents within liquid- and gel-filled cavities represents a barrier to treatment of some cancers and other pathological states. Interstitial delivery is compromised by the poor mobility of macromolecules and larger nanoscale structures. We developed an in vitro system to quantify the suitability of superparamagnetic nanoparticles (SPM NPs) as a site-specific therapeutic vehicle for delivery through fluid- and gel-based systems. SPM NP motion was induced by an external magnetic field. NP migration was modulated by NP concentration and surface coating. 135 nanometer radius PEGylated NPs moved through the extracellular matrix with an average velocity of 1.5 mm h−1, suitable for some clinical applications. Increasing the SPM NP radius to 400 nm while maintaining the same per NP magnetic susceptibility resulted in a greater than 1000-fold reduction in magnetic mobility, to less than 0.01 mm h−1. The critical influence of NP size on gel permeation was also observed in silica-coated 135 nm SPM NPs that aggregated under the experimental conditions. Aggregation played a critical role in determining the behavior of the nanoparticles. SPM NPs allow significant free-solution mobility to specific sites within a cavity and generate sufficient force to penetrate common in vivo gels.

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ACKNOWLEDGMENTS

The authors would like to acknowledge the technical assistance of R. Chen Chun-Cheng, Jordan Bush, Edwin Donnelly, Ling Geng, and Allie Fu. This study was supported by U.S. Army Medical Research and Materiel Command BCRP-CDMRP: BC023387, Vanderbilt Institute for Nanoscale Science and Engineering (VINSE), NIH grants CA58508, CA70937, CA88076, CA89674, CA89888, P50-CA90949, and Vanderbilt-Ingram Cancer Center, CCSG P30-CA68485.

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Authors and Affiliations

  1. Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, 37232-8180, USA

    Sam J. Kuhn, Dennis E. Hallahan & Todd D. Giorgio

  2. Department of Radiation Oncology, Department of Cancer Biology, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, 37232-5671, USA

    Dennis E. Hallahan

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  1. Sam J. Kuhn
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Kuhn, S.J., Hallahan, D.E. & Giorgio, T.D. Characterization of Superparamagnetic Nanoparticle Interactions with Extracellular Matrix in an in Vitro System. Ann Biomed Eng 34, 51–58 (2006). https://doi.org/10.1007/s10439-005-9004-5

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  • DOI: https://doi.org/10.1007/s10439-005-9004-5

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