Hou Rui, Lu Tianxiang, Gao Wei, Shen Jian, Yu Zheyuan, Li Datao, Zhang Ruhong, Zheng Yuanyi, Cai Xiaojun
Department of Plastic and Reconstructive Surgery, The Ninth People'S Hospital Affiliated To Shanghai Jiao Tong University School Of medicine, Shanghai, 200011, People's Republic of China.
Department of Obstetrics and Gynecology, Xijing Hospital Affiliated to the Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
ACS Nano. 2022 Jun 28;16(6):9559-9571. doi: 10.1021/acsnano.2c02832. Epub 2022 May 13.
Ischemia-reperfusion (I/R) injury leads to a low success rate of skin flap transplantation in reconstruction surgery, thus requiring development of new treatments. Necroptosis and apoptosis pathways, along with overexpression of reactive oxygen species and pro-inflammatory factors in skin flap transplantation, are deemed as potential therapeutic targets. This study provides a paradigm for nanozyme-mediated microenvironment maintenance to improve the survival rate of the transplanted skin flap. Prussian blue nanozyme (PBzyme) with multiple intrinsic biological activities was constructed and selected for this proof-of-concept study. The prepared PBzyme shows anti-inflammatory, antiapoptotic, antinecroptotic, and antioxidant activities in both and models of I/R injured skin flaps. The multiple inhibitory effects of PBzyme maintained a normal microenvironment and thus significantly promoted the survival rate of the I/R injured skin flap (from 37.21 ± 8.205% to 79.61 ± 7.5%). Of note, PBzyme regulated the expression of the characteristic signal molecules of necroptosis, including Rip 1, Rip 3, and pMLKL, indicating that PBzyme may be a therapeutic agent for necroptosis-related diseases. This study shows great prospects for clinical application of PBzyme in the treatment of skin flaps local administration.
缺血再灌注（I/R）损伤导致重建手术中皮瓣移植成功率较低，因此需要开发新的治疗方法。在皮瓣移植中，坏死性凋亡和凋亡途径，以及活性氧和促炎因子的过度表达，被视为潜在的治疗靶点。本研究为纳米酶介导的微环境维持以提高移植皮瓣的存活率提供了一个范例。构建了具有多种内在生物学活性的普鲁士蓝纳米酶（PBzyme）并将其用于本概念验证研究。所制备的PBzyme在I/R损伤皮瓣的体内和体外模型中均表现出抗炎、抗凋亡、抗坏死性凋亡和抗氧化活性。PBzyme的多种抑制作用维持了正常的微环境，从而显著提高了I/R损伤皮瓣的存活率（从37.21±8.205%提高到79.61±7.5%）。值得注意的是，PBzyme调节了坏死性凋亡特征信号分子Rip 1、Rip 3和pMLKL的表达，表明PBzyme可能是一种治疗坏死性凋亡相关疾病的药物。本研究显示了PBzyme在皮瓣局部给药治疗中的巨大临床应用前景。
