Development of a Novel Enzyme-Targeting Radiosensitizer (New KORTUC) Using a Gelatin-Based Hydrogel Instead of a Sodium Hyaluronate

Cancers

Shiho Morita-Tokuhiro¹  Yasuhiro Ogawa⁵  Norikazu Yokota⁴  Akira Tsuzuki⁴  Hideki Oda³  Naoya Ishida³  Nobutaka Aoyama¹  Akihito Nishioka¹  Zhe-Sheng (Jason) Chen² 

[1] Department of Diagnostic Radiology & Radiation Oncology, Medical school, Kochi University, Nankoku, Kochi 783-8505, Japan;;Department of Diagnostic Radiology & Radiation Oncology, Medical school, Kochi University, Nankoku, Kochi 783-8505, JapanMedical School, Kochi University, Nankoku, Kochi 783-8505, Japan;Division of Radiology, Kochi Medical School Hospital, Medical School, Kochi University, Nankoku, Kochi 783-8505, Japan;;Hyogo Prefectural Kakogawa Medical Center, Kakogawa, Hyogo 675-8555, Japan

关键词: radiosensitizer;    hydrogen peroxide;    KORTUC;    sodium hyaluronate;    hydrogel;   

DOI  :  10.3390/cancers8010010

来源: mdpi

【 摘 要 】

We recently developed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. C3H/He mice were allocated to control, KORTUC, or hydrogel groups. At 72 h after injection, each tumor was irradiated with a 6 MeV electron beam to a total dose of 30 Gy. During a 62-day observation period, changes in tumor volume and survival rates were assessed in each group. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. New KORTUC, which contains hydrogen peroxide and hydrogel, exerted a radiosensitizing effect that persisted beyond 72 h following injection of the agent. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect.

【 授权许可】

CC BY   
© 2016 by the authors; licensee MDPI, Basel, Switzerland.