Fu Zi, Zhang Meng, Huang Ying, Wang Han, Hao Wanting, Liu Zeyang, Guo Haiyan, Ni Dalong
Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
J Nanobiotechnology. 2025 May 27;23(1):384. doi: 10.1186/s12951-025-03458-z.
Persistent and intense inflammation is recognized as the primary cause of wear-particle-induced aseptic osteolysis, which ultimately resulting in aseptic prosthesis loosening. Reducing inflammation plays a significant role in mitigating osteolysis, and the STING pathway has emerged as a promising therapeutic target for its prevention. Specifically, damaged periprosthetic cells of aseptic osteolysis release double-stranded DNA (dsDNA) into the osteolytic microenvironment, serving as a specific stimulus for the STING pathway. Herein, we found that layered double hydroxide (LDH) nanozyme exhibited a robust DNA-binding capacity primarily mediated by van der Waals interactions, which showed superior performance in inhibiting dsDNA-induced inflammation of aseptic osteolysis. Importantly, such binding capability enabled effective co-loading LDH with STING inhibitor C176, thus facilitating inhibition of the STING pathway. Such synergistic actions contributed to ameliorate the inflammatory milieu and remodel the osteolysis microenvironment successfully to reduce cranial bone damage, which was confirmed on animal model of osteolysis. Collectively, this strategy demonstrated an effective approach by utilizing synergistic effects to establish a positive feedback loop in the treatment of osteolysis, thereby alleviating TiPs-induced periprosthetic osteolysis and preventing postoperative complications.
持续性和强烈炎症被认为是磨损颗粒诱导的无菌性骨溶解的主要原因，最终导致无菌性假体松动。减轻炎症在减轻骨溶解方面起着重要作用，而STING通路已成为其预防的一个有前景的治疗靶点。具体而言，无菌性骨溶解的假体周围受损细胞将双链DNA（dsDNA）释放到溶骨微环境中，作为STING通路的特异性刺激物。在此，我们发现层状双氢氧化物（LDH）纳米酶表现出强大的DNA结合能力，主要由范德华相互作用介导，在抑制dsDNA诱导的无菌性骨溶解炎症方面表现出卓越性能。重要的是，这种结合能力使LDH能够与STING抑制剂C176有效共负载，从而促进对STING通路的抑制。这种协同作用有助于改善炎症环境并成功重塑骨溶解微环境以减少颅骨损伤，这在骨溶解动物模型中得到证实。总体而言，该策略展示了一种有效的方法，即利用协同效应在骨溶解治疗中建立正反馈回路，从而减轻磨损颗粒诱导的假体周围骨溶解并预防术后并发症。
