Author(s): Melanie I'anson-Holton, Andralyn McKell, Jeffrey Okojie, Bridger Kearns, Josh Hanosek
Mentor(s): Jared Barrott
Institution BYU
Background: Antibody-drug conjugates (ADC) are burgeoning class of anti-cancer therapies. They rely on the specificity of antibodies to selectively deliver a cytotoxic payload to cancer cells expressing unique antigens. To minimize the toxicity of these ADCs, we designed a multipronged application with two separate components that by themselves are harmless, but when combined result in thermal toxicity to the tumor cells. Gold nanoparticles as the payload was one component and a near IR laser was the other. Gold nanoparticles are innocuous and exhibit localized surface plasmon resonance (LSPR). The LSPR of gold nanoparticles allows them to absorb photons at certain wavelengths, causing excitation and the release of heat. This feature allows gold nanoparticles to be used as a therapeutic tool. In this project the gold nanorods were conjugated to an anti-Oncostatin M Receptor (OSMR) antibody to target OSMR-expressing cancer cells. Thermotoxicity is induced in the cells where the conjugate resides by near IR laser activation of gold nanoparticles. Methods: Gold nanoparticles were synthesized by a seed growth method . However, the cetyltrimethylammonium bromide (CTAB) used as a capping agent to prevent aggregation of the nanorods and to enhance anisotropic growth has proven to be toxic to most cells. As such, in order to functionalize the nanorods and increase biocompatibility, the CTAB coating was replaced with m-PEG-SH. This modification was done via sonication, followed by purification using a filtration dialysis cassette. The strong affinity of the m-PEG-SH for the gold enables PEG to effectively substitute the CTAB after sonication. The gold nanorods were imaged using a transmission electron microscope (TEM), and analysed by UV-VIS spectroscopy. Results: The gold nanorods were synthesized and modified successfully. The average length and width of the unmodified gold nanorods were 21.1 nm and 6.5 nm respectively. After substituting the CTAB with PEG, the average length and width of the rods were 16.5 nm and 7.6 nm respectively. The change in dimensions can be attributed to the change in coating from CTAB to PEG. Following synthesis of the gold nanorods, they were conjugated site-specifically to a modified anti-OSMR antibody. The spectra observed after running the UV-VIS on the conjugated antibody suggest successful conjugation. Conclusion: The successful conjugation of gold nanorods to the anti-OSMR antibody suggest that using a gold-based ADC approach to target OSMR-expressing cancer cells is feasible. The laser induced gold induced thermotoxicity allows temporal control of this ADC.