Activatable MRI probes for the specific detection of bacteria

Abstract

Activatable fluorescent probes have been successfully used as molecular tools for biomedical research in the last decades. Fluorescent probes allow the detection of molecular events, providing an extraordinary platform for protein and cellular research. Nevertheless, most of the fluorescent probes reported are susceptible to interferences from endogenous fluorescence (background signal) and limited tissue penetration is expected. These drawbacks prevent the use of fluorescent tracers in the clinical setting. To overcome the limitation of fluorescent probes, we and others have developed activatable magnetic resonance probes. Herein, we report for the first time, an oligonucleotide-based probe with the capability to detect bacteria using magnetic resonance imaging (MRI). The activatable MRI probe consists of a specific oligonucleotide that targets micrococcal nuclease (MN), a nuclease derived from Staphylococcus aureus. The oligonucleotide is flanked by a superparamagnetic iron oxide nanoparticle (SPION) at one end, and by a dendron functionalized with several gadolinium complexes as enhancers, at the other end. Therefore, only upon recognition of the MRI probe by the specific bacteria is the probe activated and the MRI signal can be detected. This approach may be widely applied to detect bacterial infections or other human conditions with the potential to be translated into the clinic as an activatable contrast agent.

Nuclease Activity as a Biomarker in Cancer Detection

“…Specifically, biosensors based on nuclease-activatable oligonucleotides have been used to detect various conditions [133] such as infections [70,134,135] and cancer [67][68][69].…”

Bacteria‐Based Living Probes: Preparation and the Applications in Bioimaging and Diagnosis

“…Currently, the direct labeling of pathogens in the infection sites by imageable probes has been used to detect bacterial infections by performing in vivo bioimaging, which provides an intuitive and feasible solution for infection diagnosis and treatment. [155][156][157] Gram-negative bacteria, such as Enterobacterales, can cause severe, deep-seated infections, often leading to sepsis or even death. To create a non-invasive whole-body analysis tool that can specifically locate pathogens, Jain's group constructed a PET imaging probe on the basis of 18 F-FDS, and found that such probes could selectively distinguish Enterobacterales infection from other pathologies in mice by PET signal detection.…”

“…Currently, the direct labeling of pathogens in the infection sites by imageable probes has been used to detect bacterial infections by performing in vivo bioimaging, which provides an intuitive and feasible solution for infection diagnosis and treatment. [ 155–157 ]…”

“…For instance, Hernandez et al designed a bacteria‐based MRI probe by grafting a core superparamagnetic iron oxide nanoparticle (SPION) with S. aureus ‐specific short oligonucleotide sequences and dendrons functionalized with several gadolinium ion (Gd 3+ ) complexes. [ 156 ] As demonstrated by in vitro imaging of both S. aureus and S taphylococcus epidermidis , MRI signals could be only detected when S. aureus co‐existed with ion. Because in the presence of S. aureus , the oligonucleotides on MRI probe could be specifically cleaved by micrococcal nuclease, accompanying by the release of Gd 3+ complexes from the superparamagnetic SPION core and subsequently the activation of MRI probe.…”

Azo Reductase Activated Magnetic Resonance Tuning Probe with “Switch-On” Property for Specific and Sensitive Tumor Imaging in Vivo

“…Moreover, gadolinium oxide and superparamagnetic iron oxide complexes have been successfully applied in tumor cell imaging based on the change of their spacing after cleavage of the linker, restoring the T 1 -weighted MRI signal . This nanoscale distance-dependent phenomenon between paramagnetic “enhancer” and superparamagnetic “quencher” was later defined as magnetic resonance tuning (MRET), that is, the enhancer and the quencher are separated, resulting in a stronger T 1 MRI signal (ON state) due to the accelerated water proton relaxation by the electron spin fluctuation of the enhancer, while the enhancer and the quencher are close enough to each other, resulting in a low T 1 MRI signal (OFF state) due to the slowed water proton relaxation. , This MRET phenomenon has been employed to develop imaging contrast for imaging enzymes, sepsis, epilepsy, infection, and tumors. − As for MRET-based tumor imaging, − different MRET probes were constructed and proved to have enhanced imaging signals compared with traditional MRI contrast. However, the reported work rarely involves the early detection of tumors, which is essential to improving the cure rate of tumors.…”