Emory University scientists have mimicked the functionality found within a single-chain anti-EGFR antibody to create an artificial one. The researchers believe that such a modified anti-EGFR antibody can be used to deliver cancer-killing nanoparticles into tumor cells.
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.
From the abstract:
Epidermal growth factor receptor (EGFR) targeted nanoparticle are developed by conjugating a single-chain anti-EGFR antibody (ScFvEGFR) to surface functionalized quantum dots (QDs) or magnetic iron oxide (IO) nanoparticles. The results show that ScFvEGFR can be successfully conjugated to the nanoparticles, resulting in compact ScFvEGFR nanoparticles that specifically bind to and are internalized by EGFR-expressing cancer cells, thereby producing a fluorescent signal or magnetic resonance imaging (MRI) contrast. In vivo tumor targeting and uptake of the nanoparticles in human cancer cells is demonstrated after systemic delivery of ScFvEGFR-QDs or ScFvEGFR-IO nanoparticles into an orthotopic pancreatic cancer model. Therefore, ScFvEGFR nanoparticles have potential to be used as a molecular-targeted in vivo tumor imaging agent. Efficient internalization of ScFvEGFR nanoparticles into tumor cells after systemic delivery suggests that the EGFR-targeted nanoparticles can also be used for the targeted delivery of therapeutic agents.
Press release: Artificial Antibody Delivers Nanoparticles to Tumors
Abstract in the journal Small…
Image: Cartoon diagram of the epidermal growth factor receptor (EGFR) (rainbow colored, N-terminus = blue, C-terminus = red) complexed with its ligand epidermal growth factor (magenta) based on the PDB 1NQL crystallographic coordinates. Wikipedia
