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.
Highlights
All types of activatable probes share a unique feature, they are turned “on” only after encountering the specific target or physical stimulus, while they remain “off” in the absence of such events [1, 2]
Activatable magnetic resonance imaging (MRI) probes can overcome the limitation of fluorescence-based systems, with a mature MRI technology that offers the advantages of unlimited tissue penetration and high spatial resolution, which are exceptional features for clinical approaches [23]
Based on this knowledge and as a proof of concept study, we have designed an activatable MRI probe composed of a core superparamagnetic iron oxide nanoparticle (SPION) bearing S. aureus–specific short oligonucleotide sequences that are linked to dendrons functionalized with several gadolinium ion (Gd3+) complexes
Summary
All types of activatable probes share a unique feature, they are turned “on” only after encountering the specific target or physical stimulus, while they remain “off” in the absence of such events [1, 2]. In a previous proof-of-concept study, a molecular imaging approach that rapidly and detects S. aureus infections was reported This activatable fluorescent probe, the sequence of which is referred to as TT probe, is turned “on” by micrococcal nuclease (MN) secreted by these bacteria [27]. We have previously demonstrated the specificity of TT probe to MN secreting S. aureus among other strains and other bacteria in addition to the resistance of the probe in human and mouse serum [27] Based on this knowledge and as a proof of concept study, we have designed an activatable MRI probe composed of a core superparamagnetic iron oxide nanoparticle (SPION) bearing S. aureus–specific short oligonucleotide sequences that are linked to dendrons functionalized with several gadolinium ion (Gd3+) complexes. This work reports an efficient activatable MRI probe that exhibits high sensitivity due to high signal-to-background ratios and with unlimited tissue penetration provided by the MRI signal acquisition; these features facilitate the translation of this approach into the clinical settings
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