Conjugation of Functionalized Gadolinium Metallofullerenes with IL-13 Peptides for Targeting and Imaging Glial Tumors

Abstract

Background: Glioblastoma multiforme is the most common and most lethal primary brain tumor in humans, with median survival of approximately 1 year. Owing to the ability of glioma cells to aggressively infiltrate normal brain tissue and survive exposure to current adjuvant therapies, there is a great need for specific targeted nanoplatforms capable of delivering both therapeutic and imaging agents directly to invasive tumor cells. Method: Gadolinium-containing endohedral fullerenes, highly efficient contrast agents for MRI, were functionalized and conjugated with a tumor-specific peptide and assessed for their ability to bind to glioma cells in vitro. Results: We report the successful conjugation of the carboxyl functionalized metallofullerene Gd₃N@C₈₀(OH)_-26(CH₂CH₂COOH)_-16 to IL-13 peptides and the successful targeting ability towards brain tumor cells that overexpress the IL-13 receptor (IL-13Rα2). Conclusion: These studies demonstrate that IL-13 peptide-conjugated gadolinium metallofullerenes could serve as a platform to deliver imaging and therapeutic agents to tumor cells.

Keywords::

• brain tumor
• glioblastoma multiforme
• IL-13
• imaging
• metallofullerenes
• nanoparticle
• targeting

Financial & competing interests disclosure

This work was supported by NIH/NCI (R01 CA119371), NSF/NIRT (DMR-0507083) and Center for Innovative Technology, Commonwealth of Virginia; the Virginia Commonwealth Technology Research Fund (CTRF). Microscopy was performed at the VCU Department of Anatomy and Neurobiology Microscopy Facility, supported, in part, with funding from NIH-NINDS Center core grant (5P30NS047463). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by NIH/NCI (R01 CA119371), NSF/NIRT (DMR-0507083) and Center for Innovative Technology, Commonwealth of Virginia; the Virginia Commonwealth Technology Research Fund (CTRF). Microscopy was performed at the VCU Department of Anatomy and Neurobiology Microscopy Facility, supported, in part, with funding from NIH-NINDS Center core grant (5P30NS047463). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.