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

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, 3Depar...

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Autores principales:	Lapin NA, Vergara LA, Mackeyev Y, Newton JM, Dilliard SA, Wilson LJ, Curley SA, Serda RE
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Fullerene Intravital microscopy (IVM) Breast cancer Enhanced permeation and retention (EPR) Drug delivery Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d479eab97d8f48c6b2710ad05c19e0b6
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spelling	oai:doaj.org-article:d479eab97d8f48c6b2710ad05c19e0b62021-12-02T04:54:04ZBiotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma1178-2013https://doaj.org/article/d479eab97d8f48c6b2710ad05c19e0b62017-11-01T00:00:00Zhttps://www.dovepress.com/biotransport-kinetics-and-intratumoral-biodistribution-of-malonodiseri-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Norman 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 deliveryLapin NAVergara LAMackeyev YNewton JMDilliard SAWilson LJCurley SASerda REDove Medical PressarticleFullereneIntravital microscopy (IVM)Breast cancerEnhanced permeation and retention (EPR)Drug deliveryMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 8289-8307 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fullerene Intravital microscopy (IVM) Breast cancer Enhanced permeation and retention (EPR) Drug delivery Medicine (General) R5-920
spellingShingle	Fullerene Intravital microscopy (IVM) Breast cancer Enhanced permeation and retention (EPR) Drug delivery Medicine (General) R5-920 Lapin NA Vergara LA Mackeyev Y Newton JM Dilliard SA Wilson LJ Curley SA Serda RE Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
description	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
format	article
author	Lapin NA Vergara LA Mackeyev Y Newton JM Dilliard SA Wilson LJ Curley SA Serda RE
author_facet	Lapin NA Vergara LA Mackeyev Y Newton JM Dilliard SA Wilson LJ Curley SA Serda RE
author_sort	Lapin NA
title	Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
title_short	Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
title_full	Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
title_fullStr	Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
title_full_unstemmed	Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
title_sort	biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/d479eab97d8f48c6b2710ad05c19e0b6
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Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma

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