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Positron emission tomography (PET) guided glioblastoma targeting by a fullerene-based nanoplatform with fast renal clearance.

Abstract
Various carbonaceous nanomaterials, including fullerene, carbon nanotube, graphene, and carbon dots, have attracted increasing attention during past decades for their potential applications in biological imaging and therapy. In this study, we have developed a fullerene-based tumor-targeted positron emission tomography (PET) imaging probe. Water-soluble functionalized C60 conjugates were radio-labeled with 64Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for targeting of integrin αvβ3 in glioblastoma. The specificity of fluorescein-labeled C60 conjugates against cellular integrin αvβ3 was evaluated in U87MG (integrin αvβ3 positive) and MCF-7 cells (integrin αvβ3 negative) by confocal fluorescence microscopy and flow cytometry. Our results indicated that cRGD-conjugated C60 derivatives showed better cellular internalization compared with C60 derivatives without the cRGD attachment. Moreover, an interesting finding on intra-nuclei transportation of cRGD-conjugated C60 derivatives was observed in U87MG cells. In vivo serial PET studies showed preferential accumulation of cRGD-conjugated C60 derivatives at in U87MG tumors. In addition, the pharmacokinetic profiles of these fullerene-based nanoparticles conjugated with cRGD and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) fit well with the three compartment model. The renal clearance of C60-based nanoparticles is remarkably fast, which makes this material very promising for safer cancer theranostic applications.
STATEMENT OF SIGNIFICANCE:
Safety is one of the major concerns for nanomedicine and nanomaterials with fast clearance profile are highly desirable. Fullerene is a distinct type of zero-dimensional carbon nanomaterial with ultrasmall size, uniform dispersity, and versatile reactivity. Here we have developed a fullerene-based tumor-targeted positron emission tomography imaging probe using water-soluble functionalized C60 conjugates radio-labeled with 64Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for glioblastoma targeting. The improved tumor targeting property along with fast renal clearance behavior of C60-based nanoparticles makes this material very promising for future safer cancer theranostic applications.
AuthorsYayun Peng, Dongzhi Yang, Weifei Lu, Xiongwei Hu, Hao Hong, Ting Cai
JournalActa biomaterialia (Acta Biomater) Vol. 61 Pg. 193-203 (10 01 2017) ISSN: 1878-7568 [Electronic] England
PMID28801268 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
Chemical References
  • Copper Radioisotopes
  • Fullerenes
  • Fluorescein
Topics
  • Animals
  • Cell Line, Tumor
  • Computer Simulation
  • Copper Radioisotopes (blood, chemistry, pharmacokinetics)
  • Female
  • Fluorescein (chemistry)
  • Fullerenes (chemistry, pharmacokinetics)
  • Glioblastoma (diagnostic imaging)
  • Humans
  • Kidney (metabolism)
  • Mice, Nude
  • Nanoparticles (chemistry)
  • Positron-Emission Tomography
  • Spectroscopy, Fourier Transform Infrared
  • Time Factors
  • Tissue Distribution

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