Ratiometric optical nanoprobes enable accurate molecular detection and imaging

Abstract

Exploring and understanding biological and pathological changes are of great significance for early diagnosis and therapy of diseases. Optical sensing and imaging approaches have experienced major progress in this field. Particularly, an emergence of various functional optical nanoprobes has provided enhanced sensitivity, specificity, targeting ability, as well as multiplexing and multimodal capabilities due to improvements in their intrinsic physicochemical and optical properties. However, one of the biggest challenges of conventional optical nanoprobes is their absolute intensity-dependent signal readout, which causes inaccurate sensing and imaging results due to the presence of various analyte-independent factors that can cause fluctuations in their absolute signal intensity. Ratiometric measurements provide built-in self-calibration for signal correction, enabling more sensitive and reliable detection. Optimizing nanoprobe designs with ratiometric strategies can surmount many of the limitations encountered by traditional optical nanoprobes. This review first elaborates upon existing optical nanoprobes that exploit ratiometric measurements for improved sensing and imaging, including fluorescence, surface enhanced Raman scattering (SERS), and photoacoustic nanoprobes. Next, a thorough discussion is provided on design strategies for these nanoprobes, and their potential biomedical applications for targeting specific biomolecule populations (e.g. cancer biomarkers and small molecules with physiological relevance), for imaging the tumor microenvironment (e.g. pH, reactive oxygen species, hypoxia, enzyme and metal ions), as well as for intraoperative image guidance of tumor-resection procedures.

Regioisomeric BODIPY Benzodithiophene Dyads and Triads with Tunable Red Emission as Ratiometric Temperature and Viscosity Sensors

“…The design of ratiometric fluorescent molecular probes for temperature detection is an emerging research area that has witnessed tremendous progress in the last decade . Ratiometric temperature and viscosity molecular probes play a vital role in accurate (bio)molecular detection, sensing, imaging and theranostic applications . Such ratiometric molecular probes have low sensitivity to external factors and, thus, high spatio‐temporal resolution and accuracy .…”

“…Such ratiometric molecular probes have low sensitivity to external factors and, thus, high spatio‐temporal resolution and accuracy . Moreover, fluorescent molecular temperature/viscosity sensors are advantageous for biological applications because of their noninvasive nature . Among the various design strategies for small organic molecule based ratiometric temperature‐ and viscosity‐probes, donor‐acceptor (D‐A) rotor molecules that show twisted intramolecular charge transfer (TICT) are of particular interest .…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…Optical imaging technology, including fluorescence, PA, and Raman imaging, is a promising method for real-time IGS with great potential for broad clinical applications., [7,106,107] which can assist surgeons in performing precise operations with LN mapping and tumor localization and delineation, in identifying important adjacent structures to avoid the unintentional surgical injury, and in recognizing MRDs to ensure complete resection during operations. CAS based on CT, MRI, and even 3D reconstruction can hardly provide surgeons with intraoperative real-time imaging navigation.…”

“…[138][139][140] PAI can provide multiscale imaging ranging from organelles and individual cells to tissue, organs, and small animals; it has considerable potential for IGS and intraoperative LN mapping. [107,[144][145][146] Gold NPs, with a highest extinction coefficient, [146] have been used extensively for PAI. [143] PAI probes include conventional inorganic and organic NMs, as well as ratiometric and activatable nanoprobes.…”

Photoacoustic Probes for Molecular Detection: Recent Advances and Perspectives

“…So far, there are mainly three ways for constructions of PA probes in PAD, such as off‐on, on‐off and ratiometric strategies ( Figure a) . For off‐on strategy, after the interactions with analytes, PA probes would produce an amplified PA signal by increased light absorption, which could reduce background noise and improve the accuracy of detections.…”