BioActs offers the full spectrum of fluorescent dyes such as FSD FluorTM, Flamma® Fluors, ICG, and Other Dyes,
and also offers Fluorescent Quenchers, Crosslinkers, Fluorescent Antibodies, Bioprobes,
and Microspheres, Magnetic Beads, Dye Labeling Kit, etc.
NpFlamma® HGC series
NpFlamma® HGC series is a fluorescent dye incorporated biocompatible and biodegradable chitosan based amphiphilic nanoparticle that enables to selectively detect tumor cells. Chitosan nanoparticles can selectively accumulate in cancer tissues due to high permeability for loose new blood vessels around cancer tissues and retention effect. The polymeric nanoparticles form self-aggregates size of several hundred nanometers in the aqueous system accumulate only in vicinity of cancer tissues. Chitosan particles display low toxicity along with absence of noticeable side effect in vivo, yet they exhibit a long half-life, high stability and aqueous solubility. Thus, NpFlamma® HGC series is an ideal fluorescence agent for in vivo imaging of angiography and tumor progression. In conjunction with NIR dyes, the series allows to observe non-invasive images of cancer metastases and to contrast blood vessel. The hydrophobic nature of NpFlamma® HGC series can embed hydrophobic materials, thus they can be utilized as a selective carrier for hydrophobic cancer drugs such as doxorubicin and paclitaxel, etc. In addition, carboxylic acids on the surface of NpFlamma® HGC series can bind to a variety of biomolecules via amide or ester linkages enabling to utilize them in multi-purposes.
NpFlamma® MMP series
Matrix metalloproteinases (MMPs) are a group of calcium-dependent, zinc-containing endopeptidases that that in concert are responsible for the degradation of most extracellular matrix (ECM) proteins during organogenesis, growth and normal tissue turnover. Humans have 23 MMPs family, and the expression and activity of MMPs in adult tissues is normally quite low, but increases significantly in various pathological conditions that may lead into unwanted tissue destruction, tumor growth and metastasis, inflammatory diseases, etc. Cancer cells secrete VEGF and FGF in order to induce angiogenesis in vascular endothelial cells, but cannot reach to vascular endothelial cells as being caught in ECM. Although MMPs are connected with cancer cells survival and expansion, only very small amount of MMPs are synthetized by cancer cell. However, the cancer cells induce inflammatory cells to secrete MMPs for assisting the delivery of VEGF secreted by cancer cells and make peripheral space for angiogenesis. The connection between MMPs and apoptosis, cell migration and angiogenesis enables to utilizing MMPs as tumor markers. An increased expression and activity of MMPs in both tissues and blood of patients with various types of cancer is observed.
BioActs developed NpFlamma® MMP series, MMP-activatable polymeric in vivo fluorescent probes, for early diagnosis and for visualization of overexpressed MMPs related diseases. The probes consist of a fluorescent dye that connected to a quencher through a MMP-cleavable peptide, and a chitosan based nanoparticle (CNP). The one end of peptide is chemically conjugated to a chitosan based nanoparticle. NpFlamma® MMPs are optically silent in their inactivated state and become highly fluorescent following MMP-cleaved activation. CNP can selectively accumulate in cancer tissues due to high permeability for loose new blood vessels around cancer tissues and retention effect. The polymeric nanoparticles form self-aggregates size of several hundred nanometers in the aqueous system accumulate only in vicinity of cancer tissues. Thus, CNP enables to bring up the probe to tumor cells, and the cleavage of the peptide by MMPs allows to selective detection of tumor by realizing fluorescence imaging.
NpFlamma® MMP series equipped with several different MMPs (MMP-2, -3, -7, -9, -13) cleavable peptides that enable to detect a wide range of diseases. Since self-assembled CNPs have already been used as vehicles for hydrophobic drug delivery, and have shown therapeutic efficacy for mouse tumors. Therefore, the role of NpFlamma® MMP series might be extended as theranostic agents that simultaneously monitoring therapeutic responses and delivering therapy. BioActs offers NpFlamma® MMP series as smart fluorescent probes for monitoring MMP-related diseases such as cancer progression, invasion and metastasis, rheumatoid arthritis, pulmonary diseases and areas of cardiovascular disease, and also for evaluating the potential therapeutic efficacy of drugs targeting for these diseases.
Annexin V Flamma® series
In normal live cells, phosphatidyl serine (PS) is located on the cytoplasmic surface of the cell membrane, however PS is translocated to the outer leaflet of the plasma membrane exposing to the external cellular environment when apoptosis is in progress. Annexin V is a Ca2+ dependent PS-binding protein that has been used as a non-quantitative probe to detect cells that have expressed PS on the cell surface. Fluorescence conjugated annexin V enables to detect the externalized PS by binding to PS that exposed on the outer leaflet. BioActs developed a series of Flamma® dyes and other dyes such as FITC, TAMRA and ICG conjugated annexin V, Annexin V Flamma® series, as PS selective fluorescent probes.
Annexin V Flamma® series is a rapid and selective probe for labeling of externalized PS, an indicator of intermediate stages of apoptosis. Flamma® dyes display strong absorption, high fluorescence quantum yield and high photostability, and they maintain good fluorescence activity and stability after conjugation to biomolecules, allowing the detection of low-abundance biological structures with great sensitivity. Annexin V Flamma® conjugates can be utilized in fluorescent imaging as well as for flow cytometry of apoptotic cells, and they might be used in combination with other dyes such as propidium iodide (PI) in order to accurately analyze mixed populations of apoptotic and other cells. Annexin V Flamma® probes available as stand-alone reagent or easy-to-us kits.
Annexin V Flamma® apoptosis detection kit includes a PI nucleic acid binding dye and annexin V binding buffer. PI is impermeant to live cells and apoptotic cells, but stains dead cells with red fluorescence by binding to nucleic acids. Normal live cell is not labeled by ether Annexin V or PI, early stage apoptotic cell is stained with Annexin V and natural death or cell subject to necrosis is stained with PI. The late stage apoptotic cells are stained by both reagents. After staining a cell population with Annexin V Flamma® and PI in annexin binding buffer, apoptotic cells and dead cells can be distinguished and analyzed using a flow cytometer.
Figure 1. Annexin V Flamma® 488 cell staining
Apoptosis was induced by treating actinomycin D on HL 60 cell, and cell image was obtained after staining with Annexin V Flamma® 488 and PI in 1× Annexin V binding buffer for 15 min. Upper and lower image are same cell. Right image is fluorescence merging image, and the left figures include DIC picture. Cells labeled with green color are stained with Annexin V Flamma® 488, and red stained cells stained by PI.
Apoptosis plays an important role in the pathogenesis of a variety of diseases, such as cancer, myocardial and cerebral ischemia, and neurodegenerative diseases. Since the induction of apoptosis is an essential event in cancer treatments such as chemotherapy and irradiation, in vivo imaging of apoptosis would provide valuable information in monitoring tumor response to different therapies. As an alternative to fluorescent-conjugated proteins or antibodies, small peptide probes may serve as ideal apoptosis imaging probes. They display rapid clearance from blood circulation, efficient tissue penetration, low immunogenicity and cost-effective production. BioActs developed two series of apoptosis specific small peptide based fluorescent probes, ApoFlamma® H and ApoFlamma® PS, for effective monitoring of apoptosis. Both probes might be used alone or in combination with other dyes such as propidium iodide (PI) in order to accurately analyze mixed populations of apoptotic and other cells.
ApoFlamma® H series made up of a covalent-connection of CQRPPR hexapeptide (ApoPep) with corresponding fluorophore. ApoPep strongly binds to apoptotic and necrotic cells but weakly binds to live cells. The receptor for ApoPep was histone H1 that exposed on the surface of apoptotic cells. In necrotic cells, ApoPep entered the cells and bound to histone H1. The monitoring of tumor apoptosis in response to chemotherapy can be easily realized with optical imaging technique utilizing ApoFlamma® H series. We recommend ApoFlamma® H series as versatile fluorescent probes for in vitro and in vivo imaging of apoptosis with targeting for histone H1.
ApoFlamma® PS series enables to selectively detect phosphatidylserine (PS) on the outer leaflet of the plasma membrane. The translocation of PS from the inner to the outer leaflet of plasma membrane occurs in apoptotic cells, and PS serves as most common molecular marker for the detection and measurement of apoptotic cells under both in vitro and in vivo conditions. The PS-recognition moiety in ApoFlamma® PS series is a nonapeptide, with sequence of CLSYYPSYC, and the peptide is labeled with a fluorophore. In animal model study, ApoFlamma® PS series effectively detected tumors yet their binding to other organs such as liver and lung was negligible. BioActs recommends ApoFlamma® PS series as ideal apoptosis detecting probes for both in vitro and in vivo imaging of apoptosis with targeting of PS.
Integrins are heterodimeric transmembrane receptors for cell adhesion to extracellular matrix (ECM) proteins and play important roles in certain cell-cell adhesions. In addition, they make transmembrane connections to the cytoskeleton and activate many intracellular signaling pathways. Because of their role in tumor angiogenesis and progression, integrins have become important diagnostic and therapeutic targets. To date 24 distinct integrins are known, and among them, integrin αvβ3 is known to strongly involve in the regulation of angiogenesis. The αvβ3 is generally expressed in low levels on the epithelial cells and mature endothelial cells, but it is highly expressed in many solid tumors. The αvβ3 levels correlate well with the potential for tumor metastasis and aggressiveness, which make it an important biological target for development of antiangiogenic drugs and molecular imaging probes for early tumor diagnosis.
Cyclic tripeptide arginine-glycine-aspartate (RGD) is well-known to bind preferentially to αvβ3 integrin with high affinity. Cyclic RGD is an effective ligand for tumor targeting since integrin αvβ3 is overexpressed not only on tumoral endothelium but also on various cancer cells. Thus, targeting tumor cells or tumor vasculature by RGD-based strategies is a promising approach for delivering anticancer drugs or diagnostic agents. Cyclic RGD peptides are also able to bind αvβ5, α5β1, α6β4, α4β1, and αvβ6 integrins, which may help enhance their tumor uptake due to the increased receptor population. BioActs developed AngioFlamma® series as effective fluorescent probes for the detection of angiogenesis and tumor cells. The probes are made up of various fluorophores conjugated cyclic RGD. We offer AngioFlamma® series as in vivo fluorescent probes for imaging of blood vessels, tumors and angiogenesis.
BBB Flamma® AD is a newly developed far-red fluorescent dye enabling to detect amyloid beta (AB) plaque. AB is a key biomarker of Alzheimer disease progress, and in vivo monitoring of the marker in AB knock-in animal model study is an important issue in Alzheimer disease research. BBB Flamma® AD penetrates blood-brain barrier and selectively binds to AB plaque thereby providing real-time fluorescent AB imaging.
|NpFlamma® HGC Series||Availability :||Reacting Functionality :|
|NpFlamma® MMP Series||Availability :||Reacting Functionality :|
|Annexin V Flamma® Series||Availability :||Reacting Functionality :|
|AngioFlamma® Series||Availability :||Reacting Functionality :|
|BBBFlamma® Series||Availability :||Reacting Functionality :|