Abstract

Abstract In spite of a decreased rate of cancer onset, by about 33%, since 1991, it is still as dreadful and a major cause of death globally. After heart disease, cancer continues to be the second most prevalent cause of death in the US. According to the American Cancer Society, there will be around 2 million new cases of cancer identified in Americans in 2023, along with approximately 610,000 cancer-related deaths. Breast cancer will continue to be the most common invasive cancer diagnosed in women. Each year about 2.3 million women are diagnosed with breast cancer. In consideration of the severity of breast cancer, herein we designed and synthesized a multimode photothermal agent, FA-Hep-CuS, for the advancement of photothermal therapy of cancer. CuS nanoparticles deposited on heparin-conjugated folic acid (FA-Hep-CuS) were prepared by gently heating unfractionated heparin in dimethyl formamide (DMF), then adding N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC), and finally adding the aminated folic acid in DMF and stirring for four days. Further, FA-Hep was dispersed in DI water, then citrated CuS nanoparticles dispersed in DI water were added, and the mixture was stirred for 8 hours to prepare FA-Hep-CuS. Moreover, the activation of the nanoparticles by non-ionizing radiation (NIR; l= 808 nm) was also evaluated for increased anti-cancer efficiency. In MDA-MB-231 (Triple-negative or TNBC or ER⁻/PR⁻/Her2⁻) breast cancer cell lines, the cytotoxic effects of FA, CuS, and FA-Hep-CuS, as well as their ability to impede motility, have been investigated. They have also been examined to determine how they affect the expression of mesenchymal indicators and clonogenicity. All these demonstrated significant dose-dependent in-vitro cytotoxicity against MDA-MB- 231 breast cancer cells. The cell viability assay showed that the FA-CuS was more effective than FA and CuS. Activation of the nanoparticles with NIR resulted in the significantly enhanced dose-dependent inhibitory potential of the nanoparticles against the migratory properties of the aggressive TNBC cells. In agreement, the clonogenicity of the TNBC cells was also inhibited dose-dependently. We are now focusing on its inhibitory potential on the EMT markers of the TNBC cells. We further aim to investigate the effects of FA-Hep-CuS in in-vivo models of breast cancers. Citation Format: David Arreola. Cytotoxicity and motility inhibitory effect of FA-Hep-CuS nanoparticles on breast cancer cells [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-27-08.

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