期刊
CARBOHYDRATE POLYMERS
卷 273, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2021.118488
关键词
Carboxymethyl dextran; Nanoparticles; Sonodynamic therapy; Glutathione; Cancer therapy
资金
- Basic Science Research Program through the Na-tional Research Foundation of Korea (NRF), Republic of Korea [2018R1A2B3006080, 2020R1A6A3A01100335]
- Korea Basic Science Institute (National research Facilities and Equipment Center) - Ministry of Education [2020R1A6C101A191]
- National Research Foundation of Korea [2020R1A6C101A191, 2020R1A6A3A01100335] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
A new nanocomposite material has been developed that depletes intracellular GSH in cancer cells and induces ROS production, leading to cytotoxicity. This material has the potential to be a powerful tool in anticancer therapy.
Glutathione (GSH), a tripeptide abundant in the cancer cells, inhibits the cytotoxic effect of reactive oxygen species (ROS) and is associated with anti-apoptosis, thus facilitating tumor growth. Here, we report GSHdepleting carboxymethyl dextran nanocomposites for chemo-sonodynamic therapy for cancer. The nanocomposite is composed of the TiO2-based core as the sonosensitizer, MnO2 coat as the GSH-consuming chemosensitizer, and carboxymethyl dextran as the hydrophilic shell. The in vitro cell experiments demonstrated that, when taken up by the cancer cells, the nanocomposites can deplete intracellular GSH by reducing MnO2 to Mn2+ which induces intracellular ROS production. Upon exposure to ultrasound, the nanocomposites effectively generated cytotoxic singlet oxygen at the intracellular level, remarkably enhancing the cytotoxicity to cancer cells. Notably, chemo-sonodynamic activity of the nanocomposites induced apoptosis as well as necrosis of cancer cells, implying their high potential as the anticancer therapeutics.
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