Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

Bin'en Nie; Shicheng Huo; Xinhua Qu; Jingjing Guo; Xi Liu; Qimin Hong; You Wang; Jianping Yang; Bing Yue

doi:10.1016/j.bioactmat.2022.02.003

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

Bioact Mater. 2022 Feb 12:16:134-148. doi: 10.1016/j.bioactmat.2022.02.003. eCollection 2022 Oct.

Authors

Bin'en Nie¹, Shicheng Huo¹, Xinhua Qu¹, Jingjing Guo², Xi Liu³, Qimin Hong¹, You Wang¹, Jianping Yang², Bing Yue¹

Affiliations

¹ Department of Bone and Joint Surgery, Department of Orthopedics, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.
² State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, China.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Radiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.

Abstract

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_29-41 peptides was investigated, and bone-and-bacteria dual-targeted nanoparticles (NPs) with D6 and UBI_29-41 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 Staphylococcus aureus, 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.

Keywords: Antibacterial properties; Antibiotic treatments; BET, Brunauer-Emmett-Teller; Bone infection site targeting; CCK-8, Cell Counting Kit-8; CLSM, Confocal laser scanning microscope; FTIR, fourier transform infrared spectroscopy; MHB, Mueller-Hinton broth; MIC, minimum inhibitory concentration; MRI, magnetic resonance imaging; MRSA, methicillin-resistant Staphylococcus aureus; MSNs, mesoporous silica nanoparticles; Mesoporous silica nanoparticles; OII, Orthopedic implant-related infection; Orthopedic implants; SEM, scanning electron microscope; TEM, transmission electron microscopy; TEOS, tetraethyl orthosilicate; XRD, X-ray diffraction; rBMSCs, Rat bone marrow mesenchymal stem cells.