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Titanium dioxide (TiO2) nanoparticles have shownsuccess as photosensitizers in the form of light-based cancer therapycalled Cerenkov radiation induced therapy (CRIT). While TiO2nanoparticles have been reported to be an effective therapeutic agent,there has been little work to control their functionalization and stabilityin aqueous suspension. In this work, the controlled coating of 25 nmdiameter TiO2nanoparticles with the glycoprotein transferrin (Tf) forapplication in CRIT was demonstrated using an electrospray system.Monodisperse nanoscale droplets containing TiO2and Tf were driedduringflight, coating the proteins on the surface of the metal oxidenanoparticles. Real-time scanning mobility particle sizing, dynamic lightscattering, and transmission electron microscopy show efficient controlof the Tf coating thickness when varying the droplet size and the ratio ofTf to TiO2in the electrospray precursor suspension. Further, the functionality of Tf-coated TiO2nanoparticles wasdemonstrated, and these particles were found to have enhanced targeting activity of Tf to the Tf receptor after electrosprayprocessing. The electrospray-coated Tf/TiO2particles were also found to be more effective at killing the multiple myeloma cellline MM1.S than that of nanoparticles prepared by other reported functionalization methods. In summary, this investigation notonly provides a single-step functionalization technique for nanomaterials used in Cerenkov radiation induced therapy but alsoelucidates an electrospray coating technique for nanomaterials that can be used for a wide range of drug design and deliverypurposes.