Browse
Submit Data
Databases
API
Help

Dataset Information

33 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fluorescent Phase-Changing Perfluorocarbon Nanodroplets as Activatable Near-Infrared Probes.

ABSTRACT: The sensitivity of fluorescence imaging is limited by the high optical scattering of tissue. One approach to improve sensitivity to small signals is to use a contrast agent with a signal that can be externally modulated. In this work, we present a new phase-changing perfluorocarbon nanodroplet contrast agent loaded with DiR dye. The nanodroplets undergo a liquid-to-gas phase transition when exposed to an externally applied laser pulse. This results in the unquenching of the encapsulated dye, thus increasing the fluorescent signal, a phenomenon that can be characterized by an ON/OFF ratio between the fluorescence of activated and nonactivated nanodroplets, respectively. We investigate and optimize the quenching/unquenching of DiR upon nanodroplets' vaporization in suspension, tissue-mimicking phantoms and a subcutaneous injection mouse model. We also demonstrate that the vaporized nanodroplets produce ultrasound contrast, enabling multimodal imaging. This work shows that these nanodroplets could be applied to imaging applications where high sensitivity is required.

SUBMITTER: Spatarelu CP

PROVIDER: S-EPMC9266996 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Design and synthesis of phospholipase C and A2-activatable near-infrared fluorescent smart probes.

Project description:The primary focus of this work was to develop activatable probes suitable for in vivo detection of phospholipase activity. Phospholipases (PLs) are ubiquitous enzymes that perform a number of critical regulatory functions. They catalyze phospholipid breakdown and are categorized as A(1), A(2) (PLA(2)), C (PLC), and D (PLD) based on their site of action. Here, we report the design, synthesis, and characterization of self-quenching reporter probes that release fluorescent moieties upon cleavage with PLA(2) or PLC. A series of phospholipids were synthesized bearing the NIR fluorophore pyropheophorbide a (Pyro) at the sn-2 position. Fluorescence quenching was achieved by attachment of either a positively charged black hole quencher-3 (BHQ-3) to the phospholipid headgroup or another neutral Pyro moiety at the sn-1 position. The specificity to different phospholipases was modulated by insertion of spacers (C(6), C(12)) between Pyro and the lipid backbone. The specificity of the quenched fluorescent phospholipids was assayed on a plate reader against a number of phospholipases and compared with two commercial probes bearing the visible fluorophore BODIPY. While PyroC(6)-PyroC(6)-PtdCho revealed significant background fluorescence, and a 10% fluorescence increase under the action of PLA(2), Pyro-PtdEtn-BHQ demonstrated high selective sensitivity to PLC, particularly to the PC-PLC isoform, and its sensitivity to PLA(2) was negligible due to steric hindrance at the sn-2 position. In contrast, the C(12)-spacered PyroC(12)-PtdEtn-BHQ demonstrated a remarkable selectivity for PLA(2) and the best relative PLA(2)/PLC sensitivity, significantly outperforming previously known probes. These results open an avenue for future in vivo experiments and for new probes to detect PL activity.

| S-EPMC2958237 | biostudies-literature

Effect of Short PEG on Near-Infrared BODIPY-Based Activatable Optical Probes.

Project description:Targeted near-infrared (NIR) fluorescence probes are playing a significant role in biomedical imaging because NIR penetrates deeper into tissues and is associated with reduced autofluorescence compared to visible light fluorescence probes. Long-wavelength emitting 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) is an attractive platform for synthesizing NIR fluorophores because of its high photostability, high molar absorption coefficient, and sharp absorption and emission spectra. However, its lipophilicity hampers the conjugation chemistry necessary to add targeting moieties. In this study, we synthesized a novel NIR BODIPY derivative, NMP14. Substitutions of ethylene-bridged pyrrole units at the 3- or 5-position of the parent BODIPY chromophore result in a red shift of more than 200 nm. However, NMP14 cannot be conjugated to antibodies because of its hydrophobicity. Therefore, we synthesized NMP13 by adding short poly(ethylene glycol) to NMP14 and successfully conjugated NMP13 to cetuximab and trastuzumab. In vitro microscopic studies showed that NMP13 conjugated antibodies were activated after internalization and lysosomal processing, which means that NMP13 acts as an activatable probe only turning on after cellular internalization. After the administration of NMP13 conjugated antibodies, mice tumors were detected with high tumor to background ratios for a long period. These results suggest that NMP13 has potential as an activatable fluorescence probe for further clinical applications.

| S-EPMC7331221 | biostudies-literature

Comparison of multiple enzyme activatable near-infrared fluorescent molecular probes for detection and quantification of inflammation in murine colitis models.

Project description:BackgroundActivatable near-infrared fluorescent (NIRF) probes have been used for ex vivo and in vivo detection of intestinal tumors in animal models. We hypothesized that NIRF probes activatable by cathepsins or metalloproteinases will detect and quantify dextran sulphate sodium (DSS)-induced acute colonic inflammation in wild type mice or chronic colitis in interleukin-10 (IL-10)-null mice ex vivo or in vivo.MethodsWild type mice given DSS, water controls, and IL-10-null mice with chronic colitis were administered probes by retro-orbital injection. FMT2500 LX system imaged fresh and fixed intestine ex vivo and mice in vivo. Inflammation detected by probes was verified by histology and colitis scoring. NIRF signal intensity was quantified using 2-dimensional region of interest ex vivo or 3-dimensional region of interest analysis in vivo.ResultsEx vivo, 7 probes tested yielded significant higher NIRF signals in colon of DSS-treated mice versus controls. A subset of probes was tested in IL-10-null mice and yielded strong ex vivo signals. Ex vivo fluorescence signal with 680 series probes was preserved after formalin fixation. In DSS and IL-10-null models, ex vivo NIRF signal strongly and significantly correlated with colitis scores. In vivo, ProSense680, CatK680FAST, and MMPsense680 yielded significantly higher NIRF signals in DSS-treated mice than controls, but background was high in controls.ConclusionsBoth cathepsin or metalloproteinase-activated NIRF probes can detect and quantify colonic inflammation ex vivo. ProSense680 yielded the strongest signals in DSS colitis ex vivo and in vivo, but background remains a problem for in vivo quantification of colitis.

| S-EPMC4618379 | biostudies-literature

Activatable organic near-infrared fluorescent probes based on a bacteriochlorin platform: synthesis and multicolor in vivo imaging with a single excitation.

Project description:Near infrared (NIR) fluorescent probes are ideal for in vivo imaging because they offer deeper tissue penetration and lower background autofluorescence. Although most fluorophores in this range are cyanine-based dyes, several new classes of fluorescent NIR probes have been developed. In this study, we developed organic bacteriochlorin derivatives, NMP4 and NMP5, which are excited with a single green light and emit different narrow, well-resolved bands in the NIR (peak of 739 and 770 nm for NMP4 and NMP5, respectively). When conjugated to galactosyl-human serum albumin (hGSA) or glucosyl-human serum albumin (glu-HSA), both targeting H-type lectins, including the ?-d-galactose receptor expressing on ovarian cancer, these agents become targeted, activatable, single excitation, multicolor NIR fluorescence probes. After conjugation to either glu-HSA or hGSA, substantial quenching of fluorescence occurs that is reversed after cell binding and internalization. In vitro studies showed higher cancer cell uptake with NMP4 or NMP5 conjugated to hGSA compared to the same conjugates with glu-HSA. In vivo single excitation two-color imaging was performed after intraperitoneal injection of these agents into mice with disseminated ovarian cancer. Excited with a single green light, distinct NIR emission spectra from each fluorophore were detected and could be distinguished with spectral unmixing. In vivo results using a red fluorescence protein (RFP) labeled tumor model of disseminated ovarian cancer demonstrated high sensitivity and specificity for all probes. The success of single excitation, 2-color NIR fluorescence imaging with a new class of bacteriochlorin-based activatable fluorophores, NMP4 and NMP5, paves the way for further exploration of noncyanine dye-based NIR fluorophores.

| S-EPMC3983136 | biostudies-literature

Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents.

Project description:Microbubble (MB) contrast agents have positively impacted the clinical ultrasound (US) community worldwide. Their use in molecular US imaging applications has been hindered by their limited distribution to the vascular space. Acoustic droplet vaporization (ADV) of nanoscale superheated perfluorocarbon nanodroplets (NDs) demonstrates potential as an extravascular contrast agent that could facilitate US-based molecular theranostic applications. However these agents are metastable and difficult to manufacture with high yields. Here, we report a new formulation technique that yields reliable, narrowly dispersed sub-300 nm decafluorobutane (DFB) or octafluoropropane (OFP)-filled phospholipid-coated NDs that are stable at body temperature, using small volume microfluidization. Final droplet concentration was high for DFB and lower for OFP (>1012vs. >1010 NDs per mL). Superheated ND stability was quantified using tunable resistive pulse sensing (TRPS) and dynamic light scattering (DLS). DFB NDs were stable for at least 2 hours at body temperature (37 °C) without spontaneous vaporization. These NDs are activatable in vitro when exposed to diagnostic US pressures delivered by a clinical system to become visible microbubbles. The DFB NDs were suficiently stable to allow their processing into functionalized NDs with anti-epithelial cell adhesion molecule (EpCAM) antibodies to target EpCAM positive cells.

| S-EPMC5801773 | biostudies-literature

Ex Vivo and In Vivo Noninvasive Imaging of Epidermal Growth Factor Receptor Inhibition on Colon Tumorigenesis Using Activatable Near-Infrared Fluorescent Probes.

Project description:BackgroundNear-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection.ObjectiveTo test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in ApcMin/+ mice.MethodsThe AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and ApcMin/+ mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location.ResultsTumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo.ConclusionsThe 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.

| S-EPMC5595252 | biostudies-literature

Near-Infrared Fluorescent Probes for the Detection of Cancer-Associated Proteases.

Project description:Proteases are enzymes capable of catalyzing protein breakdown, which is critical across many biological processes. There are several families of proteases, each of which perform key functions through the degradation of specific proteins. As our understanding of cancer improves, it has been demonstrated that several proteases can be overactivated during the progression of cancer and contribute to malignancy. Optical imaging systems that employ near-infrared (NIR) fluorescent probes to detect protease activity offer clinical promise, both for early detection of cancer as well as for the assessment of personalized therapy. In this Review, we review the design of NIR probes and their successful application for the detection of different cancer-associated proteases.

| S-EPMC8383269 | biostudies-literature

Near-infrared fluorescent pH-sensitive probes via unexpected barbituric acid mediated synthesis.

Project description:Novel near-infrared pyrimidine-fused pH fluorescent probes were prepared by an unusual barbiturate-mediated debenzoindolation and subsequent heteroannulation. A plausible mechanistic pathway is proposed, and the final structures were further elucidated by 2D-NMR. All new compounds are highly fluorescent in the near-infrared region and possess excellent spectral sensitivities to environmental pH changes.

| S-EPMC2725187 | biostudies-literature

A General Strategy for Development of Near-Infrared Fluorescent Probes for Bioimaging.

Project description:Near-infrared (NIR) fluorescent dyes with favorable photophysical properties are highly useful for bioimaging, but such dyes are still rare. The development of a unique class of NIR dyes via modifying the rhodol scaffold with fused tetrahydroquinoxaline rings is described. These new dyes showed large Stokes shifts (>110?nm). Among them, WR3, WR4, WR5, and WR6 displayed high fluorescence quantum yields and excellent photostability in aqueous solutions. Moreover, their fluorescence properties were tunable by easy modifications on the phenolic hydroxy group. Based on WR6, two NIR fluorescent turn-on probes, WSP-NIR and SeSP-NIR, were devised for the detection of H2 S. The probe SeSP-NIR was applied in visualizing intracellular H2 S. These dyes are expected to be useful fluorophore scaffolds in the development of new NIR probes for bioimaging.

| S-EPMC5773255 | biostudies-literature

Pre-Assembly of Near-Infrared Fluorescent Multivalent Molecular Probes for Biological Imaging.

Project description:A programmable pre-assembly method is described and shown to produce near-infrared fluorescent molecular probes with tunable multivalent binding properties. The modular assembly process threads one or two copies of a tetralactam macrocycle onto a fluorescent PEGylated squaraine scaffold containing a complementary number of docking stations. Appended to the macrocycle periphery are multiple copies of a ligand that is known to target a biomarker. The structure and high purity of each threaded complex was determined by independent spectrometric methods and also by gel electrophoresis. Especially helpful were diagnostic red-shift and energy transfer features in the absorption and fluorescence spectra. The threaded complexes were found to be effective multivalent molecular probes for fluorescence microscopy and in vivo fluorescence imaging of living subjects. Two multivalent probes were prepared and tested for targeting of bone in mice. A pre-assembled probe with 12 bone-targeting iminodiacetate ligands produced more bone accumulation than an analogous pre-assembled probe with six iminodiacetate ligands. Notably, there was no loss in probe fluorescence at the bone target site after 24 h in the living animal, indicating that the pre-assembled fluorescent probe maintained very high mechanical and chemical stability on the skeletal surface. The study shows how this versatile pre-assembly method can be used in a parallel combinatorial manner to produce libraries of near-infrared fluorescent multivalent molecular probes for different types of imaging and diagnostic applications, with incremental structural changes in the number of targeting groups, linker lengths, linker flexibility, and degree of PEGylation.

| S-EPMC4918808 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data