Zhang Zhuodan, Cao Qiannan, Xia Yi, Cui Chunyan, Qi Ying, Zhang Qian, Wu Yuanhao, Liu Jianfeng, Liu Wenguang
School of Materials Science and Engineering, Tianjin Key Laboratory of Composite and Functional Materials, Tianjin University, Tianjin, 300350, China.
Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300192, China.
Bioact Mater. 2023 Sep 2;31:408-421. doi: 10.1016/j.bioactmat.2023.08.021. eCollection 2024 Jan.
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, 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.
术后放疗是抑制乳腺癌复发和转移的标准方法，然而放射抗性和不可避免的皮肤放射性损伤仍是乳腺癌预后中遇到的关键问题。在此，我们设计了一种可体内植入的可生物降解水凝胶和可经皮应用的抗氧化生物黏附剂，以同时预防辅助放疗后术后肿瘤复发和放射性皮肤损伤。通过连续超声诱导的β-折叠交联两亲性丝素蛋白/全氟碳/阿霉素纳米乳液形成的负载阿霉素（DOX）的可生物降解丝素蛋白/全氟碳水凝胶，在生理环境中表现出持续的氧气释放，以改善放疗的缺氧情况和敏感性，以及DOX的同步释放，最终实现有效的抗癌效果。通过α-硫辛酸和N，N-二丙烯酰基-L-赖氨酸的共聚制备了一种可拉伸生物黏附剂，并将金纳米棒和没食子酸负载到生物黏附剂中，以提供温和的光热疗法和抗氧化功能。近红外光诱导的没食子酸控释和温和的光热疗法可以有效消除放疗产生的过量自由基，并促进放射性伤口愈合。最终，动物研究证实了我们方法的有效性，其中肿瘤切除后给予水凝胶并同时应用抗氧化生物黏附贴片可有效抑制肿瘤复发并减轻皮肤放射性损伤的进展。
