Nie Bin'en, Huo Shicheng, Qu Xinhua, Guo Jingjing, Liu Xi, Hong Qimin, Wang You, Yang Jianping, Yue Bing
Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China.
Bioact Mater. 2022 Feb 12;16:134-148. doi: 10.1016/j.bioactmat.2022.02.003. eCollection 2022 Oct.
Orthopedic implants account for 99% of orthopedic surgeries, however, orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality. Current antibiotic treatments still lack the capacity to target bone infection sites, thereby resulting in unsatisfactory therapeutic effects. Here, the bone infection site targeting efficacy of D6 and UBI peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site. The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy, excellent biocompatibility and effective antibacterial properties in vitro. Furthermore, in a rat model of orthopedic implant-related infection with methicillin-resistant , the growth of bacteria was evidently inhibited without cytotoxicity, thus realizing the early treatment of implant-related infection. Hence, the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.
骨科植入物占骨科手术的99%，然而，由于存在肢体威胁性后遗症和死亡的可能性，骨科植入物相关感染是最严重的并发症之一。目前的抗生素治疗仍然缺乏针对骨感染部位的能力，从而导致治疗效果不理想。在此，研究了D6和UBI肽对骨感染部位的靶向效果，并首次制备了具有D6和UBI肽的骨-细菌双靶向纳米颗粒（NPs），以靶向骨感染部位并控制万古霉素在骨感染部位的释放。本研究结果表明，骨-细菌双靶向介孔二氧化硅纳米颗粒在体外表现出优异的骨和细菌靶向效果、良好的生物相容性和有效的抗菌性能。此外，在耐甲氧西林的骨科植入物相关感染大鼠模型中，细菌生长明显受到抑制且无细胞毒性，从而实现了植入物相关感染的早期治疗。因此，骨-细菌双靶向分子修饰的纳米颗粒可能靶向细菌感染的骨部位，并成为治疗骨科植入物相关感染的理想候选物。
