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

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dc.citation.firstpage8289
dc.citation.issueNumber12
dc.citation.journalTitleInternational Journal of Nanomedicine
dc.citation.lastpage8307
dc.citation.volumeNumber2017
dc.contributor.authorLapin, Norman A.
dc.contributor.authorVergara, Leoncio A.
dc.contributor.authorMackeyev, Yuri
dc.contributor.authorNewton, Jared M.
dc.contributor.authorDilliard, Sean A.
dc.contributor.authorWilson, Lon J.
dc.contributor.authorCurley, Steven A.
dc.contributor.authorSerda, Rita E.
dc.contributor.orgThe Smalley-Curl Institute for Nanoscale Science and Technology
dc.date.accessioned2017-12-21T18:21:51Z
dc.date.available2017-12-21T18:21:51Z
dc.date.issued2017
dc.description.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.
dc.identifier.citationLapin, Norman A., Vergara, Leoncio A., Mackeyev, Yuri, et al.. "Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma." <i>International Journal of Nanomedicine,</i> 2017, no. 12 (2017) Dove Press: 8289-8307. https://doi.org/10.2147/IJN.S138641.
dc.identifier.digitalBiotransport-kinetics
dc.identifier.doihttps://doi.org/10.2147/IJN.S138641
dc.identifier.urihttps://hdl.handle.net/1911/98910
dc.language.isoeng
dc.publisherDove Press
dc.rightsThis work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License, https://creativecommons.org/licenses/by-nc/3.0/. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/
dc.subject.keywordbreast cancer
dc.subject.keyworddrug delivery
dc.subject.keywordenhanced permeation and retention
dc.subject.keywordfullerene
dc.subject.keywordintravital microscopy
dc.titleBiotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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