In Vivo Targeting and Imaging of Tumor Vasculature with Radiolabeled, Antibody-Conjugated Nanographene

Abstract

Herein we demonstrate that nano-graphene can be specifically directed to the tumor neovasculature in vivo through targeting of CD105 (i.e. endoglin), a vascular marker for tumor angiogenesis. The covalently functionalized nano-graphene oxide (GO) exhibited excellent stability and target specificity. Pharmacokinetics and tumor targeting efficacy of the GO conjugates were investigated with serial non-invasive positron emission tomography (PET) imaging and biodistribution studies, which were validated by in vitro, in vivo, and ex vivo experiments. The incorporation of an active targeting ligand (TRC105, a monoclonal antibody that binds to CD105) led to significantly improved tumor uptake of functionalized GO, which was specific for the neovasculature with little extravasation, warranting future investigation of these GO conjugates for cancer-targeted drug delivery and/or photothermal therapy to enhance therapeutic efficacy. Since poor extravasation is a major hurdle for nanomaterial-based tumor targeting in vivo, this study also establishes CD105 as a promising vascular target for future cancer nanomedicine.

Graphene-Based Nanomaterials in Bioimaging

“…Based on this method, a number of studies have been explored. Cai and co-workers demonstrated in vivo active tumor targeting using 64 Cu labeled nGO-PEG (54). The in vivo PET imaging results evidenced the active tumor targeting by conjugating nGO-PEG with an antibody, TRC105, to target vasculatures in 4T1 murine breast tumors.…”

Recent Contributions of Elastin-Like Recombinamers to Biomedicine and Nanotechnology

“…Graphene is widely expected to prove to be a revolutionary material in the near future due to its outstanding properties, some of which, such as its high surface area, near-infrared energy absorption or highly sensitive electrical properties, are also suitable for the biomedical field and use in biomedical applications such as tumor photothermal therapy, cellular imaging, drug delivery or platforms for stem cell differentiation [150][151][152][153]. However, as we have seen previously for other materials, graphene, or graphene oxide, present two mayor drawbacks, namely their poor solubility and toxicity.…”

Radio-graphene in Theranostic Perspectives

“…Radio-graphene has been designed in various synthetic methods [22][23][24][25][26][27]. Functional moiety exposed at the edge of graphene oxide (GO) can be modified for radionuclide labeling.…”

“…Researchers have been working to find strategies for the development of in vivo active tumor targeting of graphene through the incorporation of specific ligands [26][27][28][29]. Using PET imaging, Hong et al evaluated the tumor targeting efficacy and pharmacokinetics of 66 Ga-labeled GO conjugated with TRC105 antibody that targets CD105, an ideal marker for tumor angiogenesis [26].…”

“…Targeting CD105 present in tumor neovasculature may be beneficial to tumor detection in terms of the limited extravasation of large nanoparticles. The same group also labeled a radioisotope ( 64 Cu) that has longer physical half-life (12.7 h) and TRC105 antibody onto GO before successfully determining the biodistribution, pharmacokinetics, and tumor targeting efficacy of this compound [27]. Another cancer-targeting approach using graphene was reported by Nahain, who designed a functionalized graphene by conjugating GO with photochromic dye spiropyran and hyaluronic acid (HA) [30].…”