Enhanced Drug Delivery Efficacy Using a Transferrin Variant to Target Nanoparticles

Transferrin (Tf) has been studied for several years to target drugs to cancer cells, since many cancer cells overexpress Tf receptors on their cell surfaces. However, these approaches have been limited, since native Tf has a low probability of delivering its payload due to spending only about 5 minutes inside the cell. To increase the time Tf spends with the cell, i.e., increase the cellular association of Tf, our group previously investigated variants of Tf. These modified Tf proteins were found to exhibit an increase in cellular association, which translated into an improved ability to deliver a conjugated toxin. Although molecular Tf-drug conjugates can be used for cancers that are treated locally, such as glioblastoma multiforme, they cannot be administered systemically due to competition from endogeneous Tf, which is present at a high concentration. To address this challenge, researchers have used Tf to target nanoparticles (NPs), since NPs have the ability to reach and stay at a tumor site via the enhanced permeability and retention effect. We therefore decided to expand upon this NP approach by investigating the performance of NPs decorated with a Tf variant compared to those conjugated to native Tf, since the Tf variant may also increase the cellular association of the NPs.