Probes 1 and 2 can effectively target gram-negative and gram-positive bacteria.
These compounds also preferentially stain bacteria compared to mammalian cells
[122]. In addition, detection of small numbers of bacteria would be beneficial for
early detection of inflammation. To achieve that, maltodextrin-based imaging probes
(MDPs) were designed for bacterial infection imaging in vivo, including E. coli,
P. aeruginosa, S. aureus, and B. subtilis detection [123] (see Fig. 6c). MDP could be
selectively internalized to bacterial MDPs made by conjugating a fluorescent dye to
maltohexaose so that the bacteria can be selectively internalized through maltodextrin transport pathway. This represents the first targeting strategy that can deliver an
imaging probe as low as millimolar to bacteria. Another type of MDP could
accurately image bacterial infections in rat injected with E. coli with excellent
fluorescent intensity compared to uninfected controls.
4 Prospective and Conclusions
Fluorescence imaging has emerged as a powerful tool for diagnosis and treatment
with high sensitivity, good biocompatibility, and noninvasiveness [124–
126]. Conventional imaging modalities such as CT, MRI, and radionuclide imaging involve using contrast agents that are “always on” [127]. In these cases, the
“always on” probes are not able to well distinguish the target tissues/cells and their
proximity, leading to considerable background [128]. One unique feature of
fluorescence imaging is that probes can be designed to be activatable in response
to certain biological environments such as enzymatic digestion or acidification. In
addition, compared to inorganic fluorescence probes, organic fluorescent probes
have many advantages such as larger molar extinction coefficient in the deep NIR
regions, relatively higher quantum yields, better photostability, and great biocompatibility (e.g., in zwitterionic structures and nanoformulation forms)
[129, 130]. The molecular interactions such as hydrophobic and electrostatic
interactions and hydrogen bonding between organic fluorescent dyes and biological species can lead to better sensitivity, selectivity, and bio-imaging capacity for
diagnostics [131]. While inorganic fluorescence probes have unique properties,
potential lack of body clearance and toxicity of inorganic probes may be a limiting
safety concern. For example, Cd and Pb metals show high toxicity profile, and Agand Hg-based materials need more careful assessment [132]. On the other hand,
there are also challenges and corresponding strategies for fluorescence imaging
development. For example, due to the light scattering and attenuation, fluorescence might suffer from limited depth penetration, and also it is difficult to provide
quantitative and tomographic information. Therefore, numerous multimodal imaging modalities were developed to complement each other. However, no imaging
contrast for fused imaging has been approved by the FDA yet probably because it
is still questionable whether a single probe for multimodalities is better than a
mixture of two [133].
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