Qian Ren1, Caixia Yi2, Jun Pan1, Xin Sun2, Xiao Huang2,3. 1. Key Laboratory for Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, People's Republic of China. 2. School of Sports and Health Science, Tongren University, Tongren, People's Republic of China. 3. School of Physical Education, Guangxi University of Science and Technology, Guangxi, People's Republic of China.
Abstract
Purpose: Photodynamic therapy (PDT) is a non-invasive therapeutic modality that is used for several types of cancer and involves three essential elements (light, photosensitizer (PS), and oxygen). However, clinical PS is limited by the low yield of reactive oxygen species (ROS) and a long retention time. Therefore, developing a low-cost PS that can significantly increase ROS yield in a short time is of utmost importance. Methods: In this study, brusatol (Bru) was loaded on the surface of ultraviolet A (UVA)-responsive zinc oxide (ZnO)-coated magnetic nanoparticles (Fe3O4@ZnO-Bru). The PS was well characterized by transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), a superconducting quantum interference device, and dynamic light scattering (DLS). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Hoechst staining were used to determine the inhibitory effect of Fe3O4@ZnO-Bru on squamous cell carcinoma cells (SCC) with or without UVA radiation. Intracellular ROS levels and expression of the Nrf2 signaling pathway were also determined. Results: FTIR showed that Bru was successfully loaded on Fe3O4@ZnO. Fe3O4@ZnO-Bru was superparamagnetic, and the zeta potential was 8.86 ± 0.77 mV. The Bru release behavior was controlled by UVA. Fe3O4@ZnO-Bru with UVA irradiation induced an increase of 48% ROS productivity compared to Fe3O4@ZnO-Bru without UVA irradiation, resulting in a strong inhibitory effect on SCC. Furthermore, Fe3O4@ZnO-Bru nanocomposites (Fe3O4@ZnO-Bru NCs) had nearly no toxic effect on healthy cells without UVA radiation. The released Bru could significantly inhibit the Nrf2 signaling pathway to reduce the activity of scavenging excess ROS in SCC. Conclusion: In this study, Fe3O4@ZnO-Bru was successfully synthesized. PDT was combined with photochemotherapy, which exhibited a higher inhibitory effect on SCC. It can be inferred that Fe3O4@ZnO-Bru holds great potential for skin SCC therapy.
Purpose: Photodynamic therapy (PDT) is a non-invasive therapeutic modality that is used for several types of cancer and involves three essential elements (light, photosensitizer (PS), and oxygen). However, clinical PS is limited by the low yield of reactive oxygen species (ROS) and a long retention time. Therefore, developing a low-cost PS that can significantly increase ROS yield in a short time is of utmost importance. Methods: In this study, brusatol (Bru) was loaded on the surface of ultraviolet A (UVA)-responsive zinc oxide (ZnO)-coated magnetic nanoparticles (Fe3O4@ZnO-Bru). The PS was well characterized by transmission electron microscopy (TEM), Fourier Transform infrared spectroscopy (FTIR), a superconducting quantum interference device, and dynamic light scattering (DLS). 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and Hoechst staining were used to determine the inhibitory effect of Fe3O4@ZnO-Bru on squamous cell carcinoma cells (SCC) with or without UVA radiation. Intracellular ROS levels and expression of the Nrf2 signaling pathway were also determined. Results: FTIR showed that Bru was successfully loaded on Fe3O4@ZnO. Fe3O4@ZnO-Bru was superparamagnetic, and the zeta potential was 8.86 ± 0.77 mV. The Bru release behavior was controlled by UVA. Fe3O4@ZnO-Bru with UVA irradiation induced an increase of 48% ROS productivity compared to Fe3O4@ZnO-Bru without UVA irradiation, resulting in a strong inhibitory effect on SCC. Furthermore, Fe3O4@ZnO-Bru nanocomposites (Fe3O4@ZnO-Bru NCs) had nearly no toxic effect on healthy cells without UVA radiation. The released Bru could significantly inhibit the Nrf2 signaling pathway to reduce the activity of scavenging excess ROS in SCC. Conclusion: In this study, Fe3O4@ZnO-Bru was successfully synthesized. PDT was combined with photochemotherapy, which exhibited a higher inhibitory effect on SCC. It can be inferred that Fe3O4@ZnO-Bru holds great potential for skin SCC therapy.
Authors: Dongmei Ren; Nicole F Villeneuve; Tao Jiang; Tongde Wu; Alexandria Lau; Henry A Toppin; Donna D Zhang Journal: Proc Natl Acad Sci U S A Date: 2011-01-04 Impact factor: 11.205