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酶触发组装肽修饰的磁共振调谐探针的转变用于体内细菌感染的高灵敏度成像。

Enzyme-Triggered Transforming of Assembly Peptide-Modified Magnetic Resonance-Tuned Probe for Highly Sensitive Imaging of Bacterial Infection In Vivo.

机构信息

Key Laboratory of Luminescence Analysis and Molecular Sensing, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, P. R. China.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, CAS, Beijing, 100085, P. R. China.

出版信息

Small. 2023 Jun;19(25):e2208249. doi: 10.1002/smll.202208249. Epub 2023 Mar 17.

DOI:10.1002/smll.202208249
PMID:36929641
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 (Gd ) modified MMP-2-cleavable self-assembled peptide (P ) and bacteria-targeting peptide (P), and it shows T -weighted signal due to the assemble of MNP and MRET ON phenomenon between MNP assembly and Gd . Once MPD-1 accumulates at the bacterially infected site, P included in MPD-1 is cleaved explicitly by MMP-2, which triggers the T contrast agent of MPD-1 to disassemble into the monomer of MNP, leading the recovery of T -weighted signal. Simultaneously, Gd detaches from MNP, further enhancing the T -weighted signal due to MRET OFF. The sensitive MRI of Staphylococcus aureus (low to 10 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

在早期确认细菌感染并区分无菌性炎症和细菌感染仍然是高效治疗的迫切需要。在这里,基于一种对细菌感染微环境中高度表达的基质金属蛋白酶 2(MMP-2)有反应的肽修饰磁共振调谐(MRET)探针(MPD-1),实现了体内原位高灵敏度磁共振成像(MRI)细菌感染。MPD-1 是一种组装体,由带有镧系元素离子(Gd)修饰的 MMP-2 可切割自组装肽(P)和细菌靶向肽(P)的磁性纳米颗粒(MNP)承载,由于 MNP 组装和 Gd 之间的 MRET ON 现象,它显示 T 加权信号。一旦 MPD-1 在细菌感染部位积累,包含在 MPD-1 中的 P 被 MMP-2 明确切割,这触发了 MPD-1 的 T 造影剂分解成 MNP 的单体,导致 T 加权信号的恢复。同时,Gd 从 MNP 上脱离,由于 MRET OFF,进一步增强了 T 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 10 CFU)的敏感 MRI 以及对无菌性炎症和细菌感染的准确区分表明,这种新型探针将是一种有前途的候选物,可用于高效检测体内细菌感染。

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