10th International Aerosol Conference
September 2 - September 7, 2018
America's Center Convention Complex
St. Louis, Missouri, USA

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Electrospray Functionalization of Titanium Dioxide Nanoparticles with Transferrin for Photodynamic Cancer Therapy

NATHAN REED, Ramesh Raliya, Rui Tang, Samuel Achilefu, Pratim Biswas, Washington University in St. Louis

Abstract Number: 438
Working Group: Aerosols in Medicine

Abstract
Electrospray is commonly used to produce macromolecular ions for mass spectrometry, but it has also been studied for generating monodisperse droplets for the synthesis and self-assembly of nanomaterials [1]. Most recently, electrospray has been used to generate nanoparticle standards [2], fabricate solar cells [3], and deliver nanoparticles non-invasively to the brain [4]. The techniques that enable these applications can be extended to many nanomaterials and can efficiently be used to functionalize nanoparticles in a single step. In this work, we functionalize titanium dioxide (TiO₂) nanoparticles with the protein transferrin (Tf) for application in a novel light-based cancer therapy known as Cerenkov radiation induced therapy (CRIT). Tf is a protein that can target the Tf-receptor which is known to overexpress in many types of cancer. Targeted delivery of the nanoparticles can be achieved by coating the TiO₂ with Tf protein. During CRIT treatment, by co-localizing of the PET tracers with nanophotosensitizers in diseased area, the ultraviolet light (UV) generated from β-decay of the radioisotopes can induce the generation of cytotoxic hydroxyl and superoxide radicals from the photosensitizer TiO₂ nanoparticles in vivo to achieve the therapeutic effect [5].

Using electrospray, we have controllably coated Tf on the surface of TiO₂ nanoparticles by drying monodisperse droplets of Tf and TiO₂ before collection. The coating thickness of Tf was tuned by adjusting the precursor concentration of Tf while keeping the TiO₂ number concentration constant. Scanning mobility particle sizer (SMPS) measurements closely match the expected functionalized nanoparticle size for each Tf concentration. Transmission electron microscope (TEM) images further validate this size data and show monodisperse TiO₂ nanoparticles with a coating of Tf after staining. To validate the function of the Tf is unaffected during electrospray processing, the binding affinity of Tf-coated TiO₂ to the Tf receptor was evaluated via MicroScale Thermophoresis (MST).

References:
1) Hogan Jr, Christopher J., et al. "Combined charged residue-field emission model of macromolecular electrospray ionization." Analytical Chemistry 81.1 (2008): 369-377.
2) Hogan, Christopher J., and Pratim Biswas. "Narrow size distribution nanoparticle production by electrospray processing of ferritin." Journal of Aerosol Science 39.5 (2008): 432-440.
3) Kavadiya, Shalinee, et al. "Electrospray‐Assisted Fabrication of Moisture‐Resistant and Highly Stable Perovskite Solar Cells at Ambient Conditions." Advanced Energy Materials, 1700210 (2017).
4) Raliya, Ramesh, et al. "Non-invasive aerosol delivery and transport of gold nanoparticles to the brain." Scientific Reports 7 (2017).
5) Kotagiri, Nalinikanth, et al. "Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers." Nature Nanotechnology 10.4 (2015): 370-379.