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

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 C ₆₀ conjugates were radio-labeled with ⁶⁴ Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for targeting of integrin α _v β ₃ in glioblastoma. The specificity of fluorescein-labeled C ₆₀ conjugates against cellular integrin α _v β ₃ was evaluated in U87MG (integrin α _v β ₃ positive) and MCF-7 cells (integrin α _v β ₃ negative) by confocal fluorescence microscopy and flow cytometry. Our results indicated that cRGD-conjugated C ₆₀ derivatives showed better cellular internalization compared with C ₆₀ derivatives without the cRGD attachment. Moreover, an interesting finding on intra-nuclei transportation of cRGD-conjugated C ₆₀ derivatives was observed in U87MG cells. In vivo serial PET studies showed preferential accumulation of cRGD-conjugated C ₆₀ 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 C ₆₀ -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 C ₆₀ conjugates radio-labeled with ⁶⁴ Cu and modified with cyclo (Arg-Gly-Asp) peptides (cRGD) for glioblastoma targeting. The improved tumor targeting property along with fast renal clearance behavior of C ₆₀ -based nanoparticles makes this material very promising for future safer cancer theranostic applications.
(Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)