Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix |
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Authors: | Kuhn Sam J Finch Stephanie K Hallahan Dennis E Giorgio Todd D |
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Affiliation: | Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, USA. |
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Abstract: | Steric barriers such as collagen I sharply limit interstitial delivery of macromolecular and nanoparticle (NP) based therapeutic agents. Collagenase-linked superparamagnetic NPs overcame these barriers and moved through in vitro extracellular matrix (ECM) at 90 microm h(-1), a rate similar to invasive cells, under the influence of a magnetic field. NP migration in ECM diminished linearly over 5 days. The collagenase-NP construct overcame two of the most significant barriers to nano- and microscale therapeutics deployment: proteolytic enzyme stability was maintained during a clinically useful time frame by immobilization on the NP surface and degradation of interstitial barriers to tissue biodistribution was enabled by the conjugated microbial protease. |
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