Eco‐Friendly and Scalable Synthesis of Fullerenols with High Free Radical Scavenging Ability for Skin Radioprotection

Abstract Radiation dermatitis is a common but torturous side effect during radiotherapy, which greatly decreases the life quality of patients and potentially results in detrimental cessation of tumor treatment. Fullerenol, known as “free radical sponge,” is a great choice for skin radioprotection because of its broad‐spectrum free radical scavenging performance, good chemical stability, and biosafety. In this work, a facile scalable and eco‐friendly synthetic method of fullerenols by catalyst assistant mechanical chemistry strategy is provided. As no organic solvent or high concentration of acid and alkali is introduced to this synthetic system, large‐scale (>20 g) production of fullerenols with high yield (>95%) is obtained and no complicated purification is required. Then, the skin radioprotective performance of fullerenols is systematically explored for the first time. In vitro results indicate that fullerenols significantly block the reactive oxygen species‐induced damage and enhance the viability of irradiated human keratinocyte cells. In vivo experiments suggest that medical sodium hyaluronate hydrogels loaded with fullerenols are suitable for skin administration and powerfully mitigate radiodermatitis via effectively protecting epidermal stem cells. The work not only provides an efficient gram‐scale and eco‐friendly synthetic method of fullerenols, but also promotes the development of fullerenols as potential skin radioprotectors.