Abstract:
Confirming bacterial infection at an early stage and distinguishing between sterile inflammation and bacterial infection is still highly needed for efficient treatment. Here, in situ highly sensitive magnetic resonance imaging (MRI) bacterial infection in vivo based on a peptide-modified magnetic resonance tuning (MRET) probe (MPD-1) that responds to matrix metallopeptidase 2 (MMP-2) highly expressed in bacteria-infected microenvironments is achieved. MPD-1 is an assembly of magnetic nanoparticle (MNP) bearing with gadolinium ion (Gd3+ ) modified MMP-2-cleavable self-assembled peptide (P1 ) and bacteria-targeting peptide (P), and it shows T2 -weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd3+ . Once MPD-1 accumulates at the bacterially infected site, P1 included in MPD-1 is cleaved explicitly by MMP-2, which triggers the T2 contrast agent of MPD-1 to disassemble into the monomer of MNP, leading the recovery of T1 -weighted signal. Simultaneously, Gd3+ detaches from MNP, further enhancing the T1 -weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 104 CFU) at the myositis site and accurate differentiation between sterile inflammation and bacterial infection based on the proposed MPD-1 probe suggests that this novel probe would be a promising candidate for efficiently detecting bacterial infection in vivo.
摘要:
在早期阶段确认细菌感染并区分无菌炎症和细菌感染对于有效治疗仍然非常需要。这里,基于肽修饰的磁共振调谐(MRET)探针(MPD-1)的体内原位高度敏感的磁共振成像(MRI)细菌感染,该探针响应于在细菌感染的微环境中高度表达的基质金属肽酶2(MMP-2)。MPD-1是带有钆离子(Gd3)修饰的MMP-2可切割的自组装肽(P1)和细菌靶向肽(P)的磁性纳米颗粒(MNP)的集合,由于MNP的组装和MNP组装与Gd3之间的MRETON现象,它显示了T2加权信号。一旦MPD-1在细菌感染部位积累,MPD-1中包含的P1被MMP-2明确切割,这触发MPD-1的T2造影剂分解为MNP的单体,导致T1加权信号的恢复。同时,Gd3+从MNP分离,由于MRETOFF,进一步增强了T1加权信号。基于所提出的MPD-1探针,在肌炎部位对金黄色葡萄球菌(低至104CFU)的灵敏MRI以及无菌炎症和细菌感染之间的准确区分表明,这种新型探针将是有效检测体内细菌感染的有希望的候选者。