X-ray Responsive Antioxidant Drug-Free Hydrogel for Treatment of Radiation Skin Injury

Radiotherapy (RT) is widely applied in tumor therapy, but inevitable side effects, especially for skin radiation injury, are still a fatal problem and life-threatening challenge for tumor patients. The main components of topical radiation protection preparations currently available on the market are antioxidants, such as SOD, which are limited by their unstable activity and short duration of action, making it difficult to achieve the effects of radiation protection and skin radiation damage treatment. Therefore, we designed a drug-free antioxidant hydrogel patch with encapsulated bioactive epidermal growth factor (EGF) for the treatment of radiation skin injury. The X-ray responsive hydrogel formed by copolymerization of the disulfide-containing hyperbranched poly(β-hydrazide ester) macromer polymer (PBAE), methacryloylated hyaluronic acid, and acrylamide exhibits continuous antioxidant activity through the oxidation of disulfide bonds in PBAE as well as the triggered release of EGF after X-ray responsive breakage of the polymer network to finally promote radioactive wound healing. Upon radiotherapy, the antioxidant hydrogel is able to alleviate local oxidative stress by continuously eliminating excessive ROS and can prevent deterioration of radiation skin injury. Moreover, the drug-free hydrogel with its excellent antioxidant property can overcome the disadvantages of traditional medicine (such as poor solubility, random diffusion, rapid drug clearance, and interference with tumor efficacy). Notably, the drug-free hydrogel exhibits a negligible effect for tumor therapy because the antioxidant hydrogel acts only on the epidermis and displays no shielding effect for ionization radiation. Ultimately, in vivo animal studies affirm the efficacy of our methodology, wherein the administration of the antioxidant hydrogel on acute irradiated skin attenuates the progression of radiation skin injury and promotes radioactive wound healing. This innovative strategy points out a new inspiration for the precise treatment of skin radiation damage with X-ray responsive antioxidant drug-free hydrogels.