title: Nanoparticles functionalized with collagenase exhibit improved tumor accumulation in a murine xenograft model.
abstract: Nanoparticles have garnered widespread interest for both the imaging and treatment of cancer due to their unique and tunable pharmacokinetics and their ability to carry a high payload of diverse compounds. However, despite these favorable attributes, the extent of tumor accumulation can be severely restricted due to the dense stroma surrounding the often-permeable blood vessel wall and high intratumoral pressure. In this study, we investigated whether modifying the surface of pegylated gold nanoparticles (AuNPs) with collagenase could improve the accumulation of nanoparticles within a murine tumor xenograft. It was determined that collagenase remains active after surface conjugation and the presence of collagenase has no measureable effect on cell proliferation in vitro. Following intravenous injection, the largest fractions of collagenase-labeled AuNPs were found in the liver and spleen. Histological analysis revealed no signs of toxicity in either of these organs. Blood chemistry revealed normal levels of liver enzymes, but a slightly elevated level of total bilirubin. Within the tumor, AuNPs labeled with collagenase exhibited a 35% increase in accumulation compared with unlabeled AuNPs. Therefore, these studies provide preliminary evidence that the functionalization of nanoparticles with collagenase represent an effective and safe approach to improve tumor accumulation.
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Surya
authors.initials: S
authors.lastname: Murty
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Taylor
authors.initials: T
authors.lastname: Gilliland
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Qiao
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Tate
authors.initials: T
authors.lastname: Tabtieng
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Higbee
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Ajlan
authors.initials: A
authors.lastname: Al Zaki
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Puré
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia PA, 19104 USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsourkas
keywords: collagenase; nanoparticles; penetration; stroma; tumor