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Targeting Boron Nanoparticles to the Folate Receptor in Breast Cancer Cells for Hypoxia Imaging

L Chan1*, A Rickard2 , M Zhuang3 , C Fraser3, G Palmer2 , (1) Duke Kunshan University, Suzhou, Jiangsu, (2) Duke University, Durham, NC, (3) University of Virginia, Charlottesville, VA

Presentations

(Sunday, 7/14/2019) 4:00 PM - 4:30 PM

Room: Exhibit Hall | Forum 4

Purpose: To determine the targeting ability of folic acid-conjugated boron nanoparticles to folate-receptor expressing cancer cell lines, such that this functionality can be added to existing dual-emissive boron nanoparticles for improved tumor oxygen-sensing capabilities.

Methods: A Western Blot was performed to confirm presence of the folate receptor, FOLR1, in MDA-MB-231 triple negative breast cancer cells. 2 types of single-emissive boron nanoparticles – one with folic acid conjugation (BNP+FA), one without folic acid conjugation (BNP-FA) – were incubated in varying concentrations (0%-25%) with MDA-MB-231 cells for 24 hours. Fluorescent images of the cells were captured on a fluorescence microscope and analyzed on ImageJ. After subtracting background signal, percentage of cells demonstrating boron nanoparticle uptake was determined by counting the number of cells with strong fluorescence signal. Intensity of signal was also recorded as a proxy for amount of BNP internalized into the cell. 2-way ANOVA testing was performed to determine statistical differences between the varying incubation conditions, and a linear regression was conducted to determine correlation between fluorescence intensity and BNP concentration.

Results: The Western Blot confirmed presence of FOLR1 in MDA-MB-231 cells. MDA-MB-231 cells demonstrated significantly preferential uptake of BNP+FA when compared to BNP-FA at all concentrations of BNP above 0% (p<0.0001). Uptake of BNP+FA was close, if not equal, to 100%, even at the smallest concentration of 5%. The concentration of BNP+FA also correlated to fluorescence intensity (r=0.883) – cells incubated with higher concentrations of BNP+FA showed increased fluorescence.

Conclusion: The targeting ability of BNPs conjugated with folic acid has been conclusively demonstrated. The next step is thus to conjugate our oxygen-sensing dual-emissive BNPs with folic acid for targeting purposes. This not only allows intracellular characterization of tumor oxygen tension, but also improves signal-to-noise ratio when quantifying tumor oxygen tension.

Keywords

Cell Kinetics, Hypoxia, Radiobiology

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): Bio- tissue and microenvironment

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