Recent Progress in Small‐Molecule Fluorescence and Photoacoustic Dual‐Modal Probes for the In‐Vivo Detection of Bioactive Molecules

Abstract

Intracellular bioactive molecules are essential for the maintenance of homeostasis in living organisms. Abnormal levels of them are closely related to the occurrence and development of some diseases. Hence, the direct and accurate visualization of these bioactive molecules is of vital importance for exploring their pathological roles. However, the low-content, short-lived, and widely distributed properties of bioactive molecules impede the comprehensive analysis of them dramatically. Fluorescence and photoacoustic dual-mode imaging technology provides a new solution to the above issue. Specifically, the combination of fluorescence and photoacoustic, which possesses the advantages of high resolution and in-depth tissue analysis, enables a more in-depth and systematic exploration of the pathogenic mechanisms of bioactive molecules. Moreover, due to the structural tailorability of small molecule probes, numerous small molecule dual-mode probes have been developed to meet the demand for real-time tracking and visualization of bioactive molecules in living cells or in vivo. Hence, in this review, we briefly summarize the key advances in small molecule fluorescence and photoacoustic dual-modal probes within recent years (2015)(2016)(2017)(2018)(2019)(2020)(2021). A particular focus is placed on the design strategies and biological applications of probes for the detection of various bioactive molecules in vivo. Furthermore, the challenges and further prospects in this hot field are highlighted.

Quercetin Nanoparticle-Based Hypoxia-Responsive Probe for Cancer Detection

“…Most solid tumors exhibit hypoxia, which is defined as a lack of oxygen caused by an imbalance between the rapid growth of cancer cells and new blood vessels in the tumor microenvironment. − Hypoxia has been reported to be a prognostic indicator at the time of diagnosis, regardless of clinical stage. ,, As a result, imaging of hypoxic areas is significant for identifying a tumor and determining a treatment approach. , Fluorescence-based hypoxia-responsive probes have attracted a lot of attention recently. , Some chromophores are sensitive to biological surroundings, making fluorescent probes appealing tools for studying biological interactions. − Xanthenes and cyanines have been investigated as hypoxia-sensitive probes for nitroreductase or azo reductase detection in hypoxic areas, − while dicyanomethylene-4H-pyran dyes are sensitive to cytochrome P450 reductase and nitroreductase in hypoxic tumors, , and some of these are susceptible to low pH in hypoxia. − …”

Electronic Characterization of Vis–NIR Absorbing Noninnocent Ruthenium Oxyquinolate–merocyanine Complexes and their Photoacoustic Emission in Aqueous Micellar Solution†

“…This increase in photoacoustic studies has also seen a parallel growth in the development of exogenous photoacoustic contrast agents varying across a wide spectrum of materials including molecular dyes, semiconducting polymers, carbon-based nanomaterials, plasmonic nanomaterials and hybrid nanocomposites (20)(21)(22)(23)(24)(25)(26)(27)(28). Furthermore, there is a growing trend in the development of bi-functional contrast agents, prime examples being for theranostic (photoacoustic imaging + photothermal therapy) and chemical signaling applications, such as targeted activatable photoacoustic contrast agents for biomarker recognition and binding (29)(30)(31)(32). Molecular photoacoustic contrast agents (MPACs) are of particular interest due to the structural diversity available to allow tuning of their absorption and photoacoustic properties, in addition to the improved contrast they provide by their enhanced retention and permeability (EPR) in cancer cells (33).…”

“…The majority of MPACs have been based upon organic chromophores including porphyrins, BODIPYs and extended cyanines, perylene diimides, phtaleins, xanthenes, squaraines, croconaines and curcumins, among others (20,23,29,31,32). In contrast, there has been limited attention paid to the photoacoustic properties of molecular transition metal complexes.…”

De Novo Design of Activatable Photoacoustic/Fluorescent Probes for Imaging Acute Lung Injury In Vivo

“…12,13 Thus, fluorescence and PA (FL/PA) dual-mode imaging is conducive to obtain abnormal pathological information for ALI study through highresolution imaging analysis in deep tissues. 14 In particular, activatable molecular probes can spontaneously emit signals toward specific bioindicators for real-time monitoring of pathological progression in living organisms with a high signal-to-noise ratio. 15,16 Therefore, there is an urgent desire to construct activatable FL/PA dual-mode molecular probes to accurately monitor ALI.…”

“…Acute lung injury (ALI), a pulmonary inflammatory disease induced by multiple etiological factors, can cause respiratory insufficiency and compromised lung function. , In particular, ALI progresses rapidly and commonly coexists with multiple organ dysfunction syndrome due to an uncontrolled inflammatory storm, leading to a mortality rate of 20–40%. , Therefore, real-time monitoring of pathological progression in related bio-indictors of ALI is imperative to uncover pathogenesis and ensure that patients receive diagnosis and pharmacologic intervention. − Recently, near-infrared (NIR) fluorescence imaging combined with molecular probes has attracted attention to monitor the physiological progression of various diseases, due to its benefits of noninvasive imaging ability, high sensitivity, as well as low cost. − However, the ability of NIR fluorescence imaging is limited for in vivo imaging because tissue-penetration depth is significantly compromised by emitted light scattering in tissues. Compared to fluorescence imaging, photoacoustic (PA) tomography imaging integrated with NIR excitation and ultrasonic detection can reduce emission signal scattering in tissues and result in high temporal and spatial resolution and improved tissue-penetration depth. , Thus, fluorescence and PA (FL/PA) dual-mode imaging is conducive to obtain abnormal pathological information for ALI study through high-resolution imaging analysis in deep tissues . In particular, activatable molecular probes can spontaneously emit signals toward specific bioindicators for real-time monitoring of pathological progression in living organisms with a high signal-to-noise ratio. , Therefore, there is an urgent desire to construct activatable FL/PA dual-mode molecular probes to accurately monitor ALI.…”