Antibodies that target epidermal growth factor receptor (EGFR) have proven themselves as potent anticancer drugs. Now, a team of investigators led by Shuming Nie, Ph.D., and Lily Yang, Ph.D., both at the Emory University School of Medicine and members of the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology, is aiming to capitalize on this targeting ability, using a modified anti-EGFR antibody to delivery nanoparticles into tumor cells.
Reporting its work in the journal Small, the Emory team describes its use of a so-called single-chain antibody to mimic the tumor-targeting properties of a standard anti-EGFR antibody. Standard antibodies are large biomolecules comprising two pairs of two peptide chains known as heavy and light chains. In part because of their large size, antibodies are difficult to work with and often have difficulty accessing the deeper regions of a solid tumor. To overcome these problems, the investigators built an artificial antibody comprising portions of a single heavy chain and a light chain hooked together. This construct is less than 20% of the size and weight of a full antibody, but it retains the larger molecule's binding abilities for EGFR.
With their artificial antibody in hand, the investigators used it as a tumor-targeting agent for two types of nanoparticles-quantum dots, which can be seen using fluorescence imaging, and iron oxide nanoparticles, which can be imaged using standard magnetic resonance imaging (MRI) instruments. The Emory team attached the targeting agent to the nanoparticles using a novel linking technology they developed for this purpose.
With the two types of antibody-linked nanoparticles in hand, the investigators conducted a series of experiments to determine whether these nanoscale constructs would target tumors and whether tumor cells would take up take the antibody-nanoparticle combos. Indeed, targeted nanoparticles homed in quickly on tumors when injected into tumor-bearing mice, whereas untargeted nanoparticles accumulated primarily in the liver and spleen. The targeted nanoparticles also gained rapid entry into tumor cells, whereas the untargeted nanoparticles did not. The nanoparticles were visible using both fluorescence imaging and MRI.
This work, which was detailed in the paper "Single chain epidermal growth factor receptor antibody conjugated nanoparticles for in vivo tumor targeting and imaging," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. Investigators from Ocean NanoTech, LLC, the Fox Chase Cancer Center, and the University of Washington in Seattle also participated in this study. An abstract of this paper is available at the journal's Web site. View abstract