Vision for Ratiometric Nanoprobes: In Vivo Noninvasive Visualization and Readout of Physiological Hallmarks

Abstract

Lesion areas are distinguished from normal tissues surrounding them by distinct physiological characteristics. These features serve as biological hallmarks with which targeted biomedical imaging of the lesion sites can be achieved. Although tremendous efforts have been devoted to providing smart imaging probes with the capability of visualizing the physiological hallmarks at the molecular level, the majority of them are merely able to derive anatomical information from the tissues of interest, and thus are not suitable for taking part in in vivo quantification of the biomarkers. Recent advances in chemical construction of advanced ratiometric nanoprobes (RNPs) have enabled a horizon for quantitatively monitoring the biological abnormalities in vivo. In contrast to the conventional probes whose dependency of output on single-signal profiles restricts them from taking part in quantitative practices, RNPs are designed to provide information in two channels, affording a self-calibration opportunity to exclude the analyte-independent factors from the outputs and address the issue. Most of the conventional RNPs have encountered several challenges regarding the reliability and sufficiency of the obtained data for high-performance imaging. In this Review, we have summarized the recent progresses in developing highly advanced RNPs with the capabilities of deriving maximized information from the lesion areas of interest as well as adapting themselves to the complex biological systems in order to minimize microenvironmental-induced falsified signals. To provide a better outlook on the current advanced RNPs, nanoprobes based on optical, photoacoustic, and magnetic resonance imaging modalities for visualizing a wide range of analytes such as pH, reactive species, and different derivations of amino acids have been included. Furthermore, the physicochemical properties of the RNPs, the major constituents of the nanosystems and the analyte recognition mechanisms have been introduced. Moreover, the alterations in the values of the ratiometric signal in response to the analyte of interest as well as the time at which the highest value is achieved, have been included for most of RNPs discussed in this Review. Finally, the challenges as well as future perspectives in the field are discussed.

Activatable Probes for Ratiometric Imaging of Endogenous Biomarkers In Vivo

“…However, the irreversible recognition mechanism prevents the corresponding ratiometric PA probes from participating in long-term in vivo detection of the biomarkers whose concentrations vary with microenvironmental stimuli. Therefore, it is necessary to overcome this challenge by designing a dynamic-reversible ratiometric PA probe that can effectively participate in the long term in vivo detection of biomarkers …”

Nanotechnology in inflammation: cutting-edge advances in diagnostics, therapeutics and theranostics

“…In spite of significant advancements in PA nanoprobes, accurately measuring inflammation-related biomarkers remains challenging due to their dynamic changes and short lifespans 133 , 134 . Hence, the design of highly sensitive PA nanoprobes is crucial for monitoring the complex inflammatory microenvironment.…”

Molecular imaging of tumour‐associated pathological biomarkers with smart nanoprobe: From “Seeing” to “Measuring”

“…To minimize the interference caused by passive distribution and accumulation of the nanoprobes, the ratiometric imaging strategy has been developed. [ 18 ] In comparison with the absolute fluorescent intensity dependent readout, ratiometric imaging strategy is based on at least two fluorescent signals, in which one signal can be changed under the triggering of the tumour biomarker, and the other signal can be served as a reference. Through the self‐calibration, the concentration influences of nanoprobes can be eliminated.…”

“…On the basis of the above advantages of the PA imaging, in recent years, a series of acidic‐, protease‐, and GSH‐activatable PA imaging nanoprobes have been exploited. [ 18 , 31 , 34 ] For example, Liu et al. synthesized a type of bimetallic oxide MnMoO X nanorods.…”