Coating Nanoparticles with Plant-Produced Transferrin-Hydrophobin Fusion Protein Enhances Their Uptake in Cancer Cells

Drug delivery is one of the biggest challenges in modern medicine, especially for drugs used in the treatment of cancer due to their severe side effects. Thus, new formulations are needed to enhance the delivery to specific target cells. Enclosing drugs in very small particles, called nanoparticles, is a potential solution for both increasing their solubility and controlling their delivery and release, thus diminishing the unwanted side effects. However, nanoparticles need to be stable, degradable, and reach specifically their targets. Fungal hydrophobins (HFB) are small, globular proteins that are highly soluble in water, and are able to coat insoluble drug compounds and form nanoparticles. Here, we engineered HFBs to contain transferrin, a protein that can target such nanoparticles to specific tumor cells where the drug can be released. We produced the engineered proteins in tobacco cells and found that nanoparticles were produced that were specifically taken up by cancer cells. This study provides a tool for simple one-step formulation of targeted nanoparticles for cancer therapy.