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Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma

Authors Lapin NA, Vergara LA, Mackeyev Y, Newton JM, Dilliard SA, Wilson LJ, Curley SA, Serda RE

Received 2 April 2017

Accepted for publication 21 May 2017

Published 15 November 2017 Volume 2017:12 Pages 8289—8307


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Thomas Webster

Supplementary video corresponding to image sequence, images and graphs in Figure 4 and Figure 5A and B.

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Norman A Lapin,1 Leoncio A Vergara,1,2 Yuri Mackeyev,3,4 Jared M Newton,1,5 Sean A Dilliard,6 Lon J Wilson,3,4 Steven A Curley,1 Rita E Serda1,7

1Michael E DeBakey Department of Surgery, Baylor College of Medicine, 2Institute of Biosciences & Technology, Texas A&M University, 3Department of Chemistry, Rice University, 4The Smalley-Curl Institute for Nanoscale Science and Technology, Rice University, 5Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, 6Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, 7Department of Chemical and Biological Engineering, University of New Mexico, Albuquerque, NM, USA

Abstract: [60]Fullerene is a highly versatile nanoparticle (NP) platform for drug delivery to sites of pathology owing to its small size and both ease and versatility of chemical functionalization, facilitating multisite drug conjugation, drug targeting, and modulation of its physicochemical properties. The prominent and well-characterized role of the enhanced permeation and retention (EPR) effect in facilitating NP delivery to tumors motivated us to explore vascular transport kinetics of a water-soluble [60]fullerene derivatives using intravital microscopy in an immune competent murine model of breast adenocarcinoma. Herein, we present a novel local and global image analysis of vascular transport kinetics at the level of individual tumor blood vessels on the micron scale and across whole images, respectively. Similar to larger nanomaterials, [60]fullerenes displayed rapid extravasation from tumor vasculature, distinct from that in normal microvasculature. Temporal heterogeneity in fullerene delivery to tumors was observed, demonstrating the issue of nonuniform delivery beyond spatial dimensions. Trends in local region analysis of fullerene biokinetics by fluorescence quantification were in agreement with global image analysis. Further analysis of intratumoral vascular clearance rates suggested a possible enhanced penetration and retention effect of the fullerene compared to a 70 kDa vascular tracer. Overall, this study demonstrates the feasibility of tracking and quantifying the delivery kinetics and intratumoral biodistribution of fullerene-based drug delivery platforms, consistent with the EPR effect on short timescales and passive transport to tumors.

Keywords: fullerene, intravital microscopy, breast cancer, enhanced permeation and retention, drug delivery

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