Fluorescent probes for the detection of disease-associated biomarkers

Dou, Wei‐Tao; Han, Hai-Hao; Sedgwick, Adam; Zhu, Guo-Biao; Zang, Yi; Yang, Xin‐Rong; Yoon, Juyoung; James, Tony D.; Li, Jia; He, Xiao‐Peng

doi:10.1016/j.scib.2022.01.014

Cited by 149 publications

(66 citation statements)

References 268 publications

(256 reference statements)

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“…This research offers insights into the construction of imaging probes that can target pathogen-conserved metabolic pathways, making possible the development of simple and clinically transformable fluorescent agents and materials for the timely monitoring of bacterial infections in situ . The development of fluorescent probes that can be activated by species-specific biomarkers in order to further enhance imaging precision is underway in our group. − Moreover, owing to the inherent antimicrobial properties of GO, we are also exploring the use of PABA-DCM@GO hydrogel dressing for image-guided photodynamic and/or photothermal therapy of bacterial infections. − …”

Section: Discussionmentioning

confidence: 99%

Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues

Zhong

Yang

et al. 2022

ACS Appl. Mater. Interfaces

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The ability to effectively detect bacterial infection in human tissues is important for the timely treatment of the infection. However, traditional techniques fail to visualize bacterial species adhered to host cells in situ in a target-specific manner. Dihydropteroate synthase (DHPS) exclusively exists in bacterial species and metabolically converts p-aminobenzoic acid (PABA) to folic acid (FA). By targeting this bacterium-specific metabolism, we have developed a fluorescent imaging probe, PABA-DCM, based on the conjugation of PABA with a long-wavelength fluorophore, dicyanomethylene 4H-pyran (DCM). We confirmed that the probe can be used in the synthetic pathway of a broad spectrum of Gram-positive and negative bacteria, resulting in a significantly extended retention time in bacterial over mammalian cells. We validated that DHPS catalytically introduces a dihydropteridine group to the amino end of the PABA motif of PABA-DCM, and the resulting adduct leads to an increase in the FA levels of bacteria. We also constructed a hydrogel dressing containing PABA-DCM and graphene oxide (GO), termed PABA-DCM@GO, that achieves target-specific fluorescence visualization of bacterial infection on the wounded tissues of mice. Our research paves the way for the development of fluorescent imaging agents that target species-conserved metabolic pathways of microorganisms for the in situ monitoring of infections in human tissues.

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Section: Discussionmentioning

confidence: 99%

Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues

Zhong

Yang

et al. 2022

ACS Appl. Mater. Interfaces

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“…This leads us to suggest that our sensor array could facilitate the rapid identification of an appropriate treatment for bacterial infections. 32 We anticipate that this kind of proactive therapeutic assessment could constitute an important use for illuminoceuticals such as those described here.…”

Section: ■ Introductionmentioning

confidence: 94%

Tuning the Solid- and Solution-State Fluorescence of the Iron-Chelator Deferasirox

Sedgwick

Mangel

et al. 2022

J. Am. Chem. Soc.

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Deferasirox, an FDA-approved iron chelator, has gained increasing attention for use in anticancer and antimicrobial applications. Recent efforts by our group led to the identification of this core as an easy-to-visualize aggregation-induced emission platform, or AIEgen, that provides a therapeutic effect equivalent to deferasirox (J. Am. Chem. Soc. 2021, 143, 3, 1278–1283). However, the emission wavelength of the first-generation system overlapped with that of Syto9, a green emissive dye used to indicate live cells. Here, we report a library of deferasirox derivatives with various fluorescence emission profiles designed to overcome this limitation. We propose referring to systems that show promise as both therapeutic and optical imaging agents as “illuminoceuticals”. The color differences between the derivatives were observable to the unaided eye (solid- and solution-state) and were in accord with the Commission Internationale de L’Eclairage (CIE) chromaticity diagram 1913. Each fluorescent derivative successfully imaged the respective spherical and rod shapes of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. They also displayed iron-dependent antibiotic activity. Three derivatives, ExNMe 2 (3), ExTrisT (11), and ExDCM (13), display emission features that are sufficiently distinct so as to permit the multiplex (triplex) imaging of both MRSA and P. aeruginosa via stimulated emission depletion microscopy. The present deferasirox derivatives allowed for the construction of a multi-fluorophore sensor array. This array enabled the successful discrimination between Gram-positive/Gram-negative and drug-sensitive/drug-resistant bacteria. Antibiotic sensitivity and drug-resistant mutants from clinically isolated strains could also be identified and differentiated.

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“…Among all types of FI and PDT-active agents, organic dyes are advantageous in terms of the readily tunable photophysical properties using simple structural modications. [12][13][14][15][16][17][18] However, most of the reported organic dyes suffer from aggregation-caused quenching (ACQ) in both uorescence and singlet-oxygen yield, and non-selective localization in cells. Aggregation-induced emission (AIE) was rst reported by the Tang group, 19 and describes the enhanced uorescence of organic dyes in their aggregated states.…”

Section: Introductionmentioning

confidence: 99%

Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy

Zhu

Han

et al. 2022

Chem. Sci.

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Fluorescent probes for the detection of disease-associated biomarkers

Cited by 149 publications

References 268 publications

Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues

Metabolically Specific In Situ Fluorescent Visualization of Bacterial Infection on Wound Tissues

Tuning the Solid- and Solution-State Fluorescence of the Iron-Chelator Deferasirox

Molecularly engineered AIEgens with enhanced quantum and singlet-oxygen yield for mitochondria-targeted imaging and photodynamic therapy

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