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Increased nanoparticle penetration in collagenase-treated multicellular spheroids

Authors Thomas T Goodman, Peggy L Olive, Suzie H Pun

Published 15 July 2007 Volume 2007:2(2) Pages 265—274

Thomas T Goodman1, Peggy L Olive2, Suzie H Pun1

1Department of Bioengineering, University of Washington, Seattle, WA, USA; 2BC Cancer Research Centre, Vancouver, BC, Canada

Abstract: The extracellular matrix of solid tumors presents a transport barrier that restricts nanoparticle penetration, thereby limiting the efficacy of nano-sized delivery vehicles for cancer imaging and therapy. In this study, the effect of nanoparticle size and collagenase treatment on penetration of carboxylated polystyrene nanoparticles was systematically assessed in a multicellular spheroid model. Penetration of the nanoparticles into the spheroid core was limited to particles smaller than 100 nm. Collagenase treatment of spheroids resulted in significantly increased penetration of nanoparticles up to 100 nm with only a minor increase in particle penetration observed for particles larger than 100 nm. Collagenase was immobilized onto the surface of nanoparticles for site-specific degradation of ECM proteins. Collagenase-coated, 100 nm nanoparticles demonstrated a 4-fold increase in the number of particles delivered to the spheroid core compared with control nanoparticles. Thus, nanoparticle delivery to solid tumors may be substantially improved by the incorporation of ECM-modulating enzymes in the delivery formulation.

Keywords: nanoparticles, collagenase, cancer treatment, spheroids, solid tumors

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