Combination of biodegradable hydrogel and antioxidant bioadhesive for treatment of breast cancer recurrence and radiation skin injury

Abstract

Postoperative radiotherapy is the standard method for inhibition of breast cancer recurrence and metastasis, whereas radiation resistant and ineluctable skin radiation injury are still key problems encountered in the prognosis of breast cancer. Herein, we design an internally implantable biodegradable hydrogel and extracutaneously applicable antioxidant bioadhesive to concurrently prevent postoperative tumor recurrence and radioactive skin injury after adjuvant radiotherapy. The biodegradable silk fibroin/perfluorocarbon hydrogel loading doxorubicin (DOX) formed by consecutive ultrasonication-induced β-sheets-crosslinked amphiphilic silk fibroin/perfluorocarbon/DOX nanoemulsion, exhibits continuous release of oxygen in physiological environment to improve hypoxia and sensitivity of radiotherapy, as well as simultaneous release of DOX to finally achieve effective anti-cancer effect. A stretchable bioadhesive is fabricated by copolymerization of α-thioctic acid and N, N-diacryloyl-l-lysine, and gold nanorods and gallic acid are loaded into the bioadhesive to afford gentle photothermal therapy and antioxidant functions. The near-infrared light-induced controlled release of gallic acid and mild photothermal therapy can efficiently eliminate excess free radicals generated by radiotherapy and promote radioactive wound healing. Ultimately, in vivo animal studies substantiate the efficacy of our methodology, wherein the post-tumor resection administration of hydrogel and concomitant application of an antioxidant bioadhesive patch effectively inhibit tumor recurrence and attenuate the progression of skin radiation damage.