Enzyme-activated apoptotic bodies-encapsulated NSET biomimetic probe for wash-free detection of intracellular pathogen in synovial fluid and monitoring therapy effect of septic arthritis

Abstract

The survival of Staphylococcus aureus (S. aureus) within host cells leads to recurrences of septic arthritis after conventional treatment, which is a challenging clinical problem. Simple, rapid and sensitive detection of intracellular bacteria in septic arthritis synovial fluid and real-time monitoring of antibiotic efficacy for septic arthritis are important to the management of this disease. Herein, an enzyme-responsive activated nanoparticle surface energy transfer (NSET) biomimetic probe (FP1Au@AB) constructed with a fluorescent polypeptide (FP1)-gold nanoparticle (AuNPs, Au) complex (FP1Au) coated with apoptotic body (AB) was applied to detect intracellular S. aureus in septic arthritis synovial fluid from clinical samples and monitor the treatment of antibiotic of rifampicin (Rif) to septic arthritis in mouse models. The as-prepared NSET bionic probes of FP1Au@AB bears AB coating which makes the probes are of good actively targeting to macrophages, and the probes could be specifically tailored by caspase-1 presented in infected macrophages, resulting fluorescent signal on. Based on the FP1Au@AB probe, the detection of intracellular bacteria in synovial fluid with a low detection limit of 5 (the average number of S. aureus in one host cell) was realized without the need of washing extracellular bacteria beforehand. Additionally, therapy efficacy of septic arthritis in mouse model could be monitored timely based the proposed probe. Moreover, FP1Au@AB probes could be applied to confirm whether the synovial fluid from patients with septic arthritis contained intracellular bacteria or not, which is benefit for the doctor to do the administration. The FP1Au@AB probe-based lighting up analytical method shows great potential for the administration and evaluation of therapy of septic arthritis in clinic.