Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix.
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.
Kuhn
Sam J
SJ
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee 37235, USA.
Finch
Stephanie K
SK
Hallahan
Dennis E
DE
Giorgio
Todd D
TD
D000818:Animals; D002417:Cattle; D017364:Collagenases / Q000737:chemistry* / Q000528:radiation effects; D004574:Electromagnetic Fields; D005109:Extracellular Matrix / Q000737:chemistry* / Q000502:physiology / Q000528:radiation effects; D007103:Immobilization; D066298:In Vitro Techniques; D049329:Nanostructures / Q000737:chemistry* / Q000528:radiation effects; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000528:radiation effects; D013499:Surface Properties; D013997:Time Factors
D012710:Serum Albumin, Bovine; D017364:Collagenases