| Autor: |
Lee HY; Department of Radiological Science, Dong-Eui University, Pusan 47340, Republic of Korea., Park JS; Interdisciplinary Program of Perfume and Cosmetic, Chonnam National University, Gwangju 61186, Republic of Korea., Kim TG; Wellesley College, 106 Central Street, Wellesley, MA 02481, USA., Kim T; College of Arts and Sciences, University of Pennsylvania, 20 Cohen Hall, 249 South 36th St, Philadelphia, PA 19104, USA., Kim DH; Tyros Biotechnology Inc., 75 Kneeland St. 14 Floors, Boston, MA 02111, USA., Yun J; Jeonnam Bio Foundation (JBF), Food Research Center, Naju City 58275, Jeonnam, Republic of Korea., Jeong YI; Department of Dental Materials, College of Dentistry, Chosun University, Gwangju 61452, Republic of Korea. |
| Abstrakt: |
The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with the amine group of chitosan oligosaccharide (COS) using a thioketal linker (COSthBSO) to liberate BSO and chlorine e6 (Ce6) under oxidative stress, and then, Ce6-COSthBSO NP (Ce6-COSthBSO NP), fabricated by a dialysis procedure, showed an accelerated release rate of BSO and Ce6 by the addition of hydrogen peroxide, indicating that nanophotosensitizers have ROS sensitivity. In the in vitro cell culture study using HCT116 colon carcinoma cells, a combination of BSO and Ce6 efficiently suppressed the intracellular GSH and increased ROS production compared to the sole treatment of Ce6. In particular, Ce6-COSthBSO NP showed higher efficacy in the suppression of GSH levels and ROS production compared to the free Ce6 and Ce6/BSO combination. These results were due to the fact that Ce6-COSthBSO NP was efficiently delivered to the intracellular region, suppressed intracellular GSH levels, and elevated ROS levels. The in vivo animal tumor xenograft study demonstrated Ce6-COSthBSO NP being efficiently delivered to the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was higher than those of other organs. The combination of Ce6 and BSO efficiently suppressed tumor growth compared to the sole treatment of Ce6, indicating that BSO might efficiently suppress GSH levels and increase ROS levels in the tumor microenvironment. Specifically, Ce6-COSthBSO NP showed the strongest performance in inhibition of tumor growth than those of Ce6 or the CE6/BSO combination, indicating that they were efficiently delivered to tumor tissue, increased ROS levels, and then efficiently inhibited tumor growth. We suggest that COSthBSO nanophotosensitizers are promising candidates for PDT treatment of cancer cells. |
