AUTHOR=Mochizuki Chihiro , Kayabe Yukihito , Nakamura Junna , Igase Masaya , Mizuno Takuya , Nakamura Michihiro TITLE=Surface Functionalization of Organosilica Nanoparticles With Au Nanoparticles Inhibits Cell Proliferation and Induces Cell Death in 4T1 Mouse Mammary Tumor Cells for DNA and Mitochondrial-Synergized Damage in Radiotherapy JOURNAL=Frontiers in Chemistry VOLUME=10 YEAR=2022 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2022.907642 DOI=10.3389/fchem.2022.907642 ISSN=2296-2646 ABSTRACT=

Radiotherapy is one of the most effective cancer treatments. Au nanoparticles (NPs) are one of the most used X-ray sensitizing materials however the effective small sub-nm size of Au NPs used for X-ray sensitizers is disadvantageous for cellular uptake. Here, we propose the surface functionalization of organosilica NPs (OS) with Au NPs (OS/Au), which combined the 100 nm size of OS and the sub-nm size of Au NPs, and synthesized effective Au materials as an X-ray sensitizer. The X-ray sensitizing potential for 4T1 mouse mammary tumor cells was revealed using a multifaceted evaluation combined with a fluorescence microscopic cell imaging assay. The number of polyethyleneimine (PEI)-modified OS (OS/PEI) and OS/Au (OS/Au/PEI) uptake per 4T1 mouse mammary tumor cell was the same; however, 4T1 cells treated with OS/Au/PEI exhibited significant inhibition of cell proliferation and increases in cell death by X-ray irradiation at 8Gy. The non-apoptotic death of OS/Au/PEI-treated 4T1 cells was increased by DNA and mitochondrial-synergized damage increase and showed potential applications in radiotherapy.