Development of radiolabeled metal chalcogenide nanoparticles for targeted radiotherapy against an infection
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI SYSTEM AT AUTHOR'S REQUEST.] Targeted radiotherapy has been demonstrated to be therapeutic against infections with doses comparable to what a patient would receive for cancer treatment. The aim of this research to create a platform for targeted radiotherapy against tuberculosis, a lung-based infection of growing concern due to emerging drug resistant strains. Instead of a traditional bifucntional chelate approach, a copper sulfide (CuS) nanoparticle radiolabeled with [subscript 35]S was chosen. A nanoparticle would enhance the uptake in the lung as past work in the Robertson group has demonstrated. The long half-life of [subscript 35]S could allow for the nanoparticle to act like a brachytherapy source at the infection site if it is internalized and trapped inside the infection site. Copper sulfide's NIR absorption peak can also be used for photothermal ablation therapy against the infection site. The copper sulfide nanoparticles also have innate antimicrobial properties that can be used to arrest bacterial growth. Copper sulfide has a K[subscript sp] of 6x10[subscript -37], suggesting the nanoparticle will be very stable. Radiolabeling results with [subscript 35]S were promising with 99.4[plus or minus]0.6 % (n = 3) of the activity being incorporated into the nanoparticle. Stability in DI water was poor with over 50% of the activity escaping from the nanoparticle over the course of two weeks. The source of this degradation was identified as sulfide in the nanoparticle oxidizing. Literature indicated that to enhance stability of the nanoparticle it needed to be capped with an inert material such as zinc sulfide. The need of capping with an inert material to improve activity retention was demonstrated with Cu-In-S nanoparticles. It was found that the Cu-In-S was highly susceptible to degradation by oxidization. Solution radiostability studies lost over 50% of the activity in air within a week as sulfide oxidized to sulfate. Conversely when the solution stability study was performed under argon, only 8% of the activity was lost from the core. When the core nanoparticle was sufficiently shelled with ZnS activity solution retention was improved, with only 5% of the activity escaping the core/shell nanoparticles over two weeks in air. Future studies will aim to investigate the killing effects of the nanoparticle and targeted radiotherapy in vitro against Mycobacterium smegmatis, a nonpathogenic surrogate of the genus that can be used in biosafety level 1 laboratories.
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