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 α_vβ₃ in glioblastoma. The specificity of fluorescein-labeled C₆₀ conjugates against cellular integrin α_vβ₃ was evaluated in U87MG (integrin α_vβ₃ positive) and MCF-7 cells (integrin α_vβ₃ 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. 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.