Near-infrared Fluorescence Signal Research Articles

Calcium-binding near-infrared fluorescent nanoprobe for bone tissue imaging

We report a self-assembled calcium-binding nanoprobe which emits a near-infrared fluorescence (NIRF) signal. We have designed a calcium-binding NIRF nanoprobe by chemically coupling alendronate (ALN), a specific targeting ligand, and NIRF-emitting Cy5.5-labeled dibenzocyclooctyne, to the two respective ends of azide-polyethylene glycol-NHS ester. Prepared ALN-PEG-Cy5.5 forms the self-assembled nanostructures and has high affinity for calcium phosphates-containing bone minerals. In addition, ALN-PEG-Cy5.5 can be employed to visualize intracellular calcium ion levels in vitro as well as normal bone tissues in vivo. These results suggest that our calcium-binding NIRF nanoprobe has a promising potential for calcium imaging in vitro and in vivo.

Targeted NIRF/MR dual-mode imaging of breast cancer brain metastasis using BRBP1-functionalized ultra-small iron oxide nanoparticles.

Tumor metastasis to brain is the main clinical manifestation of patients with advanced breast cancer, leading to poor survival prognosis. In order to detect the early incidence of brain metastasis, it is urgent to develop hypersensitive contrast agents for multimode imaging. In this study, PEG-phospholipids coated, a phage play derived peptide, BRBP1 peptide modified ultra-small iron oxide nanoparticles were prepared for targeted NIRF and MR imaging of breast cancer brain metastasis. The nanoparticles showed 10nm core-shell, high relaxivity values and photon emission efficiency in vitro. The nanoparticles offered a T2 contrast imaging effect and near-infrared fluorescent signal enhancement. Compared with control peptide modified nanoparticles, the MR/NIRF imaging signal of BRBP1-modified nanoparticles in tumor tissue was significantly enhanced, which should be induced by the targeting ability of BRBP1 peptide. These results indicated that BRBP1-SPIO@mPEG (DiR) nanoparticles could be applied as an effective targeted delivery system for diagnosis of breast cancer brain metastasis.

(Invited) Evolution of Synthetic Molecular Recognition on Single Walled Carbon Nanotubes

Molecular recognition is fundamental to the design of therapeutics, diagnostics, and sensors. Many of these sensor technologies rely on natural or synthetic molecular recognition elements such as antibodies and aptamers, which have evolved to be highly selective for their molecular targets. However, there are numerous applications for which existing approaches to molecular recognition have been unable to generate optical probes, particularly for neuromodulators and neuropeptides. Herein, we describe a polymer evolution-based platform, in which 10^12 unique polynucleotide polymers are adsorbed to single-walled carbon nanotubes (SWNT). The SWNT-pinned polynucleotide polymers can be screened for their ability to bind a target analyte and provide a selective near-infrared fluorescence signal. Iterative selection of analyte-binding polymers that form a SWNT-surface-adsorbed phase for target recognition are identified through ionic desorption of sub-optimal polymers, and exponential amplification of synthetic polymers that recognize the target analyte. Next-generation sequencing identifies SWNT-polynucleotide conjugates with sequences selective and sensitive for the desired analyte. We demonstrate the utility of this platform for the evolution of SWNT-polymer nanosensors for neuromodulators [1] and neuropeptides, and discuss its potential for identification of chirality-specific SWNT separation. Our results suggest our platform is fundamentally generic in enabling the evolution of nanosensors from synthetic polymer-nanoparticle conjugates for any desired analyte. 1. Jeong, S., Yang, D., Beyene, A.G., O’Donnell, J.T.D., Gest, A. M., Navarro, N., Sun, X., Landry, M.P. High Throughput Evolution of Near Infrared Serotonin Nanosensors. Science Advances (2019). DOI: 10.1101/673152

Activatable Fluorescence Imaging of Macrophages in Cerebral Aneurysms Using Iron Oxide Nanoparticles Conjugated With Indocyanine Green.

Background and PurposeChronic inflammation is involved in the formation and enlargement of cerebral aneurysms (CAs), with macrophages playing a key role in the process. The present study evaluated visualization of macrophages present in CAs using an activatable fluorescent probe (IONP-ICG) comprising an iron oxide nanoparticles (IONPs) conjugated with indocyanine green (ICG).MethodsIONP-ICG was intravenously administered to 15-week-old CA model rats (n = 8), and ex vivo near-infrared fluorescence (NIRF) imaging and histological assessment of exposed CAs and cerebral arteries were performed 48 h later. Similar evaluations were performed in the control group, which included CA model rats given IONPs or ICG (n = 8 each).ResultsICG-derived NIRF signals were detected in three IONP-ICG group rats but not in IONP or ICG control groups. Among the three rats that exhibited signals, NIRF signal accumulation was observed in the CA of two rats and at the site of hemodynamic stress in the left posterior cerebral artery in one rat. Histologically, NIRF signals correlated strongly with macrophage localization. A total of 13 CAs formed in the IONP-ICG group. The number of macrophages in the CA wall was significantly greater in the two CAs that exhibited NIRF signals compared to the remaining 11 CAs that did not (P = 0.037). Moreover, all 11 CAs that did not exhibit NIRF signals were iron-negative, while the two CAs that exhibited NIRF signals were both iron-positive (P = 0.013).ConclusionNIRF imaging using an activatable IONP-ICG probe is feasible for detecting the macrophage-rich regions in CAs and the cerebral artery wall, which is considered an early lesion in the process of CA formation.

Activatable Molecular Probes for Second Near-Infrared Fluorescence, Chemiluminescence, and Photoacoustic Imaging.

Optical imaging plays a crucial role in biomedicine. However, due to strong light scattering and autofluorescence in biological tissue between 650-900 nm, conventional optical imaging often has a poor signal-to-background ratio and shallow penetration depth, which limits its ability in deep-tissue in vivo imaging. Second near-infrared fluorescence, chemiluminescence, and photoacoustic imaging modalities mitigate these issues by their respective advantages of minimized light scattering, eliminated external excitation, and ultrasound detection. To enable disease detection, activatable molecular probes (AMPs) with the ability to change their second near-infrared fluorescence, chemiluminescence, or photoacoustic signals in response to a biomarker have been developed. This Minireview summarizes the molecular design strategies, sensing mechanisms, and imaging applications of AMPs. The potential challenges and perspectives of AMPs in deep-tissue imaging are also discussed.

Detection of Mediastinal Lymph Node Metastases Using Indocyanine Green (ICG) Fluorescence Imaging in an Orthotopic Implantation Model.

The method of quickly identifying metastatic mediastinal lymph nodes has become an urgent problem for lung cancer surgery. Indocyanine green (ICG) has the characteristic of being retained in or around the lymph nodes; its pharmacokinetic characteristics and optimal imaging time have not yet been elucidated. The IVIS Lumina Imaging System was used to detect near infrared (NIR) fluorescence signals at different ICG doses, times and excitation/emission wavelengths in vitro. An artificial lymphogenous metastatic model of squamous lung carcinoma was established in 32 SCID-CB17 mice using Ma44.3 cells. An intratracheal injection of 1.25 ml/kg ICG (1.25×10-2 mg/ml) was performed, then 780 nm Ex and 845 nm Em were used to visualize ICG at four different times. The metastatic mediastinal lymph nodes and the implanted local tumor site in the left lung were confirmed with bioluminescence and hematoxylin and eosin (H&E) staining of pathological specimens. ICG had the strongest NIR fluorescence signal when using 780 nm Ex and 845 nm Em at 2 to 4 h after administrating 1.25×10-2 mg/ml ICG in vitro. Combined with pathological H&E examination, fluorescence imaging of ICG reflected true-positive mediastinal metastasis of the mediastinum at 0.5 h and 2 h after the injection of ICG in vivo. While true-positive local tumor growth at the site of implantation in the left lung was reflected within 4 h after the injection of ICG. ICG was able to display the metastatic mediastinal lymph nodes within 2 h after endotracheal injection in an orthotopic squamous lung carcinoma implantation model.

Cover Picture: An Activatable Polymeric Reporter for Near‐Infrared Fluorescent and Photoacoustic Imaging of Invasive Cancer (Angew. Chem. Int. Ed. 18/2020)

An activatable polymeric reporter (P-Dex) was designed to turn on near-infrared fluorescence and photoacoustic signals in response to a biomarker (uPA) for in vivo imaging of invasive breast cancers, as reported by Q. Miao, K. Pu et al. in their Research Article on page 7018. P-Dex not only has a high sensitivity and specificity towards the cancer biomarker but also undergoes renal clearance in living mice.

An Activatable Polymeric Reporter for Near‐Infrared Fluorescent and Photoacoustic Imaging of Invasive Cancer

AbstractDiscriminative detection of invasive and noninvasive breast cancers is crucial for their effective treatment and prognosis. However, activatable probes able to do so in vivo are rare. Herein, we report an activatable polymeric reporter (P‐Dex) that specifically turns on near‐infrared (NIR) fluorescent and photoacoustic (PA) signals in response to the urokinase‐type plasminogen activator (uPA) overexpressed in invasive breast cancer. P‐Dex has a renal‐clearable dextran backbone that is linked with a NIR dye caged with an uPA‐cleavable peptide substrate. Such a molecular design allows P‐Dex to passively target tumors, activate NIR fluorescence and PA signals to effectively distinguish invasive MDA‐MB‐231 breast cancer from noninvasive MCF‐7 breast cancer, and ultimately undergo renal clearance to minimize the toxicity potential. Thus, this polymeric reporter holds great promise for the early detection of malignant breast cancer.

An Activatable Polymeric Reporter for Near-Infrared Fluorescent and Photoacoustic Imaging of Invasive Cancer.

Discriminative detection of invasive and noninvasive breast cancers is crucial for their effective treatment and prognosis. However, activatable probes able to do so in vivo are rare. Herein, we report an activatable polymeric reporter (P-Dex) that specifically turns on near-infrared (NIR) fluorescent and photoacoustic (PA) signals in response to the urokinase-type plasminogen activator (uPA) overexpressed in invasive breast cancer. P-Dex has a renal-clearable dextran backbone that is linked with a NIR dye caged with an uPA-cleavable peptide substrate. Such a molecular design allows P-Dex to passively target tumors, activate NIR fluorescence and PA signals to effectively distinguish invasive MDA-MB-231 breast cancer from noninvasive MCF-7 breast cancer, and ultimately undergo renal clearance to minimize the toxicity potential. Thus, this polymeric reporter holds great promise for the early detection of malignant breast cancer.

Fluoro-Photoacoustic Polymeric Renal Reporter for Real-Time Dual Imaging of Acute Kidney Injury.

Photoacoustic (PA) imaging agents detect disease tissues and biomarkers with increased penetration depth and enhanced spatial resolution relative to traditional optical imaging, and thus hold great promise for clinical applications. However, existing PA imaging agents often encounter the issues of slow body excretion and low-signal specificity, which compromise their capability for in vivo detection. Herein, a fluoro-photoacoustic polymeric renal reporter (FPRR) is synthesized for real-time imaging of drug-induced acute kidney injury (AKI). FPRR simultaneously turns on both near-infrared fluorescence (NIRF) and PA signals in response to an AKI biomarker (γ-glutamyl transferase) with high sensitivity and specificity. In association with its high renal clearance efficiency (78% at 24 h post-injection), FPRR can detect cisplatin-induced AKI at 24 h post-drug treatment through both real-time imaging and optical urinalysis, which is 48 h earlier than serum biomarker elevation and histological changes. More importantly, the deep-tissue penetration capability of PA imaging results in a signal-to-background ratio that is 2.3-fold higher than NIRF imaging. Thus, the study not only demonstrates the first activatable PA probe for real-time sensitive imaging of kidney function at molecular level, but also highlights the polymeric probe structure with high renal clearance.

Gram‐Positive Bacteria Cell Wall Driven Self‐Disassembled Nanovesicles against Methicillin‐Resistant Staphylococcus Aureus

AbstractIn the delivery system, high‐performance targeting and local burst‐releasing of antibiotics enable the enhancement of antipathogen efficacy and reduction of drug‐resistance risk. Bacteria cell wall driven self‐disassembled nanovesicles (BSNs) composed of a dense H‐aggregated cyanine bilayer are herein reported. The nanovesicle displays the trigger‐disassembly and turn‐on near infrared (NIR) fluorescence property activated by Gram‐positive bacteria. Mechanistic studies indicate that the interaction between nanovesicles and lipoteinchoic acid within the bacterial cell wall disrupts nanovesicles and the free cyanine molecules insert into the network of peptidoglycan, which brings recovered fluorescence. Meanwhile, owing to the burst release of the oritavancin antibiotic payload inside the nanovesicle, the minimum inhibitory concentration of oritavancin is significantly reduced by fourfold compared to that of the free one. Intriguingly, this smart nanoantibiotic effectively enhances the defense against methicillin‐resistant Staphylococcus aureus both in vitro and in vivo, meanwhile the NIR fluorescence signal enables quantitative bioimaging of the therapuetic outcome.

A Renal‐Clearable Macromolecular Reporter for Near‐Infrared Fluorescence Imaging of Bladder Cancer

AbstractBladder cancer (BC) is a prevalent disease with high morbidity and mortality; however, in vivo optical imaging of BC remains challenging because of the lack of cancer‐specific optical agents with high renal clearance. Herein, a macromolecular reporter (CyP1) was synthesized for real‐time near‐infrared fluorescence (NIRF) imaging and urinalysis of BC in living mice. Because of the high renal clearance (ca. 94 % of the injection dosage at 24 h post‐injection) and its cancer biomarker (APN=aminopeptidase N) specificity, CyP1 can be efficiently transported to the bladder and specially turn on its NIRF signal to report the detection of BC in living mice. Moreover, CyP1 can be used for optical urinalysis, permitting the ex vivo tracking of tumor progression for therapeutic evaluation and easy translation of CyP2 as an in vitro diagnostic assay. This study not only provides new opportunities for non‐invasive diagnosis of BC, but also reveals useful guidelines for the development of molecular reporters for the detection of bladder diseases.

A Renal-Clearable Macromolecular Reporter for Near-Infrared Fluorescence Imaging of Bladder Cancer.

Bladder cancer (BC) is a prevalent disease with high morbidity and mortality; however, in vivo optical imaging of BC remains challenging because of the lack of cancer-specific optical agents with high renal clearance. Herein, a macromolecular reporter (CyP1) was synthesized for real-time near-infrared fluorescence (NIRF) imaging and urinalysis of BC in living mice. Because of the high renal clearance (ca. 94 % of the injection dosage at 24 h post-injection) and its cancer biomarker (APN=aminopeptidase N) specificity, CyP1 can be efficiently transported to the bladder and specially turn on its NIRF signal to report the detection of BC in living mice. Moreover, CyP1 can be used for optical urinalysis, permitting the ex vivo tracking of tumor progression for therapeutic evaluation and easy translation of CyP2 as an in vitro diagnostic assay. This study not only provides new opportunities for non-invasive diagnosis of BC, but also reveals useful guidelines for the development of molecular reporters for the detection of bladder diseases.

High performance one-for-all phototheranostics: NIR-II fluorescence imaging guided mitochondria-targeting phototherapy with a single-dose injection and 808 nm laser irradiation

Current phototheranostics is still encountering various impediments, which causes complicated and prolonged therapy, and increases unnecessary side effects and systemic toxicity to patients. Herein, mitochondria-targeting one-for-all phototheranostic nanoparticles based on single-component organic molecule were designed and fabricated. After being irradiated with a single 808 nm laser, outstanding second near-infrared (NIR-II) fluorescence signals (with a high fluorescence quantum yield of 2.2% in water) were obtained for NIR-II fluorescence imaging, which could efficiently locate tumor and real-time monitor the therapeutic process. Moreover, such nanoparticles also presented superb photothermal conversion efficiency (39.6%) and singlet oxygen yield (2.3%, almost 12 times higher than clinical NIR dye indocyanine green) under 808 nm laser illumination, which could produce both potent hyperthermia and abundant singlet oxygen, resultantly leading to the mitochondrial dysfunction and further cell apoptosis. Both in vitro and in vivo investigations demonstrated that such nanoagents displayed significantly tumor theranostic efficacy, resulting from single 808 nm laser triggered high performance NIR-II fluorescence imaging guided mitochondria-targeting phototherapy. It was noteworthy that only a single-dose injection and 808 nm laser irradiation were employed during in vivo treatment. We believe that the phototheranostic nanoparticles developed in this work will open up a new dimension in cancer theranostics.

Targeting MMP-14 for dual PET and fluorescence imaging of glioma in preclinical models

There is a clinical need for agents that target glioma cells for non-invasive and intraoperative imaging to guide therapeutic intervention and improve the prognosis of glioma. Matrix metalloproteinase (MMP)-14 is overexpressed in glioma with negligible expression in normal brain, presenting MMP-14 as an attractive biomarker for imaging glioma. In this study, we designed a peptide probe containing a near-infrared fluorescence (NIRF) dye/quencher pair, a positron emission tomography (PET) radionuclide, and a moiety with high affinity to MMP-14. This novel substrate-binding peptide allows dual modality imaging of glioma only after cleavage by MMP-14 to activate the quenched NIRF signal, enhancing probe specificity and imaging contrast. MMP-14 expression and activity in human glioma tissues and cells were measured in vitro by immunofluorescence and gel zymography. Cleavage of the novel substrate and substrate-binding peptides by glioma cells in vitro and glioma xenograft tumors in vivo was determined by NIRF imaging. Biodistribution of the radiolabeled MMP-14-binding peptide or substrate-binding peptide was determined in mice bearing orthotopic patient-derived xenograft (PDX) glioma tumors by PET imaging. Glioma cells with MMP-14 activity showed activation and retention of NIRF signal from the cleaved peptides. Resected mouse brains with PDX glioma tumors showed tumor-to-background NIRF ratios of 7.6-11.1 at 4 h after i.v. injection of the peptides. PET/CT images showed localization of activity in orthotopic PDX tumors after i.v. injection of 68Ga-binding peptide or 64Cu-substrate-binding peptide; uptake of the radiolabeled peptides in tumors was significantly reduced (p < 0.05) by blocking with the non-labeled-binding peptide. PET and NIRF signals correlated linearly in the orthotopic PDX tumors. Immunohistochemistry showed co-localization of MMP-14 expression and NIRF signal in the resected tumors. The novel MMP-14 substrate-binding peptide enabled PET/NIRF imaging of glioma models in mice, warranting future image-guided resection studies with the probe in preclinical glioma models.

A unique off-on near-infrared QCy7-derived probe for selective detection and imaging of hydrogen sulfide in cells and invivo.

Hydrogen sulfide (H2S) has been found to be an important biological regulator that plays important roles in many physiological and pathological processes. Near-infrared (NIR) fluorescent probes capable of selectively detecting H2S invivo will be useful tools to understand its mechanisms in biological processes. Herein, we reported an easily synthesized and stimuli-responsive NIR fluorescent probe (QCy7-HS) for selective evaluation of endogenous H2S in the living cells and mice. In response to cellular H2S stimulus, QCy7-HS is converted to QCy7 and shows a unique off-on near-infrared fluorescence signal change. The results of selectivity and kinetic studies indicated that our probe has high H2S binding capacity. Therefore, this probe was used for the fluorescence detection of H2S in cells. Moreover, the probe was applied for study exogenous and endogenous H2S in live mice, indicating that the new probe can be used as an efficient tool on H2S related events in living animals.

Peptide-Driven Targeted Drug-Delivery System Comprising Turn-On Near-Infrared Fluorescent Xanthene-Cyanine Reporter for Real-Time Monitoring of Drug Release.

Targeted drug delivery (TDD) is an efficient strategy for cancer treatment. However, the real-time monitoring of drug delivery is still challenging because of a pronounced lack of TDD systems capable of providing a near-infrared (NIR) fluorescence signal for the detection of drug-release events. Herein, a new TDD system, comprising a turn-on NIR fluorescent reporter attached to an anticancer drug and targeting peptide, is reported. This system provides both TDD and NIR fluorescence monitoring of drug-release events in target tissue. In this TDD system, a new carboxy-derivatized xanthene-cyanine (XCy) dye is attached to an anticancer drug, chlorambucil (CLB), through a hydrolytically cleavable ester linker and coupled to a targeting peptide, octreotide amide (OCTA), which is specific to somatostatin receptors SSTR-2 and STTR-5 overexpressed on many tumor cells. This OCTA-G-XCy-CLB (G: γ-aminobutyric acid) conjugate exhibits no detectable fluorescence, whereas, upon the hydrolytic cleavage of the ester linker, a bright NIR fluorescence appears at λ≈710 nm; this signals release of the drug. Real-time TDD monitoring is demonstrated for the example of the human pancreatic cancer cell line overexpressing SSTR-2 and STTR-5, in comparison with the noncancerous Chinese hamster ovary cell line, which contains a reduced number of these receptors.

Self‐Amplified Drug Delivery with Light‐Inducible Nanocargoes to Enhance Cancer Immunotherapy

Chemoimmunotherapy by systemic administration of individual regimens suffers from inconsistent pharmacokinetics profiles, low tumor specificity, and severe side effects. Despite promising nanoparticle-based codelivery approaches in therapeutics, the pathophysiological barriers of solid tumors are a hurdle for tumor accumulation and deep penetration of the drug-loaded nanoparticles. A light-inducible nanocargo (LINC) for immunotherapy is reported. LINC is composed of a reduction-responsive heterodimer of photosensitizer pheophorbide A (PPa) and indoleamine 2,3-dioxygenase 1 (IDO-1) inhibitor, i.e., NLG919, and a light-activatable prodrug of oxaliplatin (OXA). LINC administrated through intravenous injection is passively accumulated at the tumor site to generate near-infrared (NIR) fluorescence signal. Under fluorescence imaging guidance, the first-wave of NIR laser irradiation induce reactive oxygen species (ROS) generation, trigger cleavage of the polyethylene glycol (PEG) corona, and thus promote tumor retention and deep penetration of LINC. When exposed to the second-wave NIR laser illumination, LINC efficiently elicits the immune response and promotes intratumoral infiltration of cytotoxic T lymphocytes (CTLs). Furthermore, NLG919 delivered by LINC reverses the immunosuppressive tumor microenvironment by suppressing IDO-1 activity. Chemoimmunotherapy with LINC inhibit the tumor growth, lung metastasis, and tumor recurrence. The light-inducible self-amplification strategy for improved drug delivery and immunotherapy shows potential.

Abstract 1399: Ex-vivo targeting of urothelial carcinomas by fluorescent pHLIP imaging agents

Abstract Introduction: The detection of urothelial carcinomas of the bladder and upper tract is not satisfactory. Incomplete findings by contemporary imaging modalities provide a challenge in patient care, so there is a definitive need to improve diagnosis and treatment methods for urothelial carcinomas. Experimental procedures: ICG (indocyanine green) near infrared fluorescent (NIRF) dyes were conjugated with a pH-Low Insertion Peptide (pHLIP®), which senses and targets the acidity at the surfaces of cancer cells. In a few cases IR800 pHLIP® was used. Urinary neoplasm (kidney, ureter and bladder) specimens obtained through radical surgery were irrigated and incubated ex-vivo with ICG pHLIP® followed by fluorescence imaging. Pathology findings were correlated with the ICG pHLIP® NIRF imaging. Results: In the upper urothelial tract, nine of ten patients with nephroureterectomy had urothelial carcinomas (UTUC). Eighteen (100%) malignant lesions were found in NIRF imaging. Only thirteen (72%) of malignant lesions were found under white light macroscopic examination. ICG pHLIP® NIRF imaging gave a 28% increase in diagnosis of UTUC in ex-vivo specimens. There was no non-specific uptake in the non-tumoral tissue. The ICG pHLIP® imaging agent identified malignant upper tract urothelial lesions with 100% specificity and sensitivity. In the lower urinary tract, thirty-eight radical cystectomy specimens were incubated with pHLIP® conjugated with one of the NIRF dyes (ICG or IR800). In the thirty-eight bladders, eighty-one lesions were identified using fluorescent pHLIP®(specificity (97%) and sensitivity (100%)). White light cystoscopy did not detect 20.5% of lesions identified under NIRF cystoscopy (p&amp;lt;.001). Normal tissue did not show any uptake by the construct; however, entrapment of the dye in the necrotic tumor bed was noted. All regions showing the NIRF signal of pHLIP® were confirmed by standard pathological analysis. Conclusions: The ICG pHLIP® NIRF revealed additional lesions not seen with white light ex-vivo cystoscopy or preoperative ureteroscopy. pHLIP® based agents promise to improve diagnostic accuracy for urothelial carcinomas and may enable targeted treatment. Citation Format: Borivoj Golijanin, Anna Moshnikova, Donald M. Engelman, Oleg A. Andreev, Yana K. Reshetnyak, Ali Amin, Dragan Golijanin. Ex-vivo targeting of urothelial carcinomas by fluorescent pHLIP imaging agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1399.

A water-soluble near-infrared fluorescent probe for sensitive and selective detection of cysteine

A near-infrared (NIR) fluorescent probe (Cys-AN) for selective and sensitive detection of cysteine (Cys) was designed and synthesized. The fluorescent probe was water-soluble and had a large Stokes shift of 150 nm, whose detection limit could reach to 0.96 μM in PBS buffer. After we analyzed the HRMS, TLC and optical data, a proposed sensing mechanism for the detection of Cys could result from the Michael addition and intramolecular cyclization reactions between the probe and Cys, followed by intramolecular charge transfer (ICT) process to afford the NIR fluorescent signal at 674 nm. Meanwhile, Cys-AN exhibited low cytotoxicity, and was successfully applied for bioimaging of Cys in living cells.