Biodegradable zinc-containing mesoporous silica nanoparticles for cancer therapy
S. Chen, Sarah L. Greasley, Zhan Yuin Ong, Parichart Naruphontjirakul, Samuel J. Page, John V. Hanna, Andia N. Redpath, Olga Tsigkou, Sara M. Rankin, Mary P. Ryan, Alexandra E. Porter, Julian R. Jones
Abstract
Triple-negative breast cancers are extremely aggressive with limited treatment options because of the reduced response of the cancerous cells to hormonal therapy. Here, monodispersed zinc-containing mesoporous silica nanoparticles (MSNPs-Zn) were produced as a tuneable biodegradable platform for delivery of therapeutic zinc ions into cells. We demonstrate that the nanoparticles were internalized by cells, and a therapeutic dose window was identified in which the MSNPs-Zn were toxic to breast cancer cells but not to healthy epithelial (MCF-10a) cells or to murine macrophages. A significant reduction in the viability of triple negative MDA-MB-231 and MCF-7 (ER+) breast cancer cells was seen following 24 h exposure to MSNPs-Zn. The more aggressive MDA-MB-231 cells, with higher metastatic potential, were more sensitive to MSNPs-Zn than the MCF-7 cells. MSNPs-Zn underwent biodegradation inside the cells, becoming hollow structures, as imaged by high-resolution transmission electron microscopy. The mesoporous silica nanoparticles provide a biodegradable vehicle for therapeutic ion release inside cells.