Multi-Modal Imaging Monitored M2 Macrophage Targeting Sono-Responsive Nanoparticles to Combat MRSA Deep Infections

Abstract

Sijie Chen,1,2,* Jiahao Wang,3– 6,* Kui Tang,1,2 Haiqin Liao,1,2 Yan Xu,1,2 Long Wang,3– 6 Chengcheng Niu1,2 1Department of Ultrasound Diagnosis, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Research Center of Ultrasonography, the Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 4Hunan Engineering Research Center of Biomedical Metal and Ceramic Implants, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 5National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6Hunan Key Laboratary of Aging Biology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chengcheng Niu, Department of Ultrasound Diagnosis, the Second Xiangya Hospital, Central South University, Changsha, 410011, People’s Republic of China, Email [email protected]: MRSA with high morbidity and mortality is prone to cause serious infection, SDT has become a new antibiotic-free modality for bacterial infection treatment. Switching from proinflammatory M1 macrophages to anti-inflammatory M2 macrophages dominant could activate the immune system to generate an anti-infection immune response.Methods: Herein, we developed M2 macrophages derived cell membranes coated PLGA nanoparticles with IR780 encapsulation (M2/IR780@PLGA) for antibacterial SDT and subsequent M2 macrophage polarization to enhance the therapeutic efficacy of MRSA myositis. For in situ visualization of antibacterial SDT, both diagnostic high-frequency US and magnetic resonance imaging (MRI) were introduced to monitor the sono-therapeutic progression of M2/IR780@PLGA nanoparticles in mice with bacterial myositis.Results: Our developed M2/IR780@PLGA nanoparticles exhibited excellent antibacterial effects due to the IR780 under low-frequency US irradiation in vitro. In an MRSA-infected mice model, a great deal of M2/IR780@PLGA nanoparticles accumulated at the site of inflammation due to M2 macrophage coating. The infected legs in the M2/IR780@PLGA nanoparticles-based SDT group were significantly smaller, fewer blood flow signals, a slight muscular edema without obvious intermuscular abscesses under high-frequency US and MR images guidance. Histopathology proved the infected legs in the M2/IR780@PLGA nanoparticles-mediated SDT group had less clumped bacteria infiltration, more M2 macrophage expression and less M1 macrophage expression. The percentage of mature dendritic cells in spleens was much higher in the group of mice with M2/IR780@PLGA nanoparticles-based SDT.Conclusion: This study provides a promising nanoparticles-based SDT anti-bacterial strategy, which could effectively enhance the antibacterial SDT and subsequent promote M2 macrophage polarization to boost the therapeutic efficacy of MRSA myositis.Keywords: M2 macrophage, sonodynamic therapy, multidrug-resistant bacterial infections, antibacterial therapy, reactive oxygen species

Keywords

• m2 macrophage
• sonodynamic therapy
• multidrug-resistant bacterial infections
• antibacterial therapy
• reactive oxygen species