53 results about "Cytolysosome" patented technology

The present invention is directed to methods and systems for the treatment of inborn genetic errors or other defects that cause deficiencies of active enzymes or proteins within the cells of the central nervous system. Such methods and systems generally comprise an implantable catheter system designed for the chronic delivery of specially formulated proteins to intrathecal, intracerebroventricular, and / or intraparenchymal regions of the central nervous system. The invention has application in the neuropathic aspects of the broad category of lysosomal storage diseases. These genetic based diseases are the result of insufficient enzyme activity to catabolize specific substances, which thereby accumulate in the cellular lysosomes.

The invention discloses a fluorescent probe for detecting formaldehyde in a cytolysosome and a preparation method thereof. The chemical name of the fluorescent probe is 4-hydrazino-N-(2-morpholinyl ethyl)naphthalimide. The fluorescence intensity of the fluorescent probe is remarkably enhanced along with the increase of the formaldehyde content. The fluorescent probe is utilized to detect the content of formaldehyde in cells through a fluorescence imaging technology, particularly the content of formaldehyde in the cytolysosome, and can be used for evaluating and studying physiological functions of formaldehyde in the cells.

The invention provides a fluorescent probe for selectively detecting hypochlorous acid. A weakly-alkaline morpholine structure is introduced onto a naphthalimide fluorescent matrix so that the probe can be positioned into a cytolysosome, a selenide structure is introduced as an active center reacting with hypochlorous acid, hypochlorous acid can be selectively detected by using the fluorescent difference between the reactant and the product, and particularly, the probe can be used for detecting hypochlorous acid in living cytolysosome.

The invention relates to a fluorescent probe which can directly detect hypochlorite in lysosome on the basis of 1,8-naphthalimide and a preparation method and application of the fluorescent probe. The fluorescent probe has the molecular structure as shown in (I), is simple to synthesize, can selectively detect hypochlorite ions in a pure PB buffer solution and can resist interference from other active oxygen small molecules. Besides, by use of the fluorescent probe, color changes of the solution can be observed with naked eyes and also can be observed under an ultraviolet lamp. The fluorescent probe can also be used for detecting hypochlorite ions in the cytolysosome, is short in response time and low in limit of detection and has a potential application value.

The invention belongs to the technical field of analysis and detection, and provides a lysosome-targeted Cys near-infrared fluorescent probe and a preparation method and application thereof. The near-infrared fluorescent probe is 3-(2-(3-(dicyanomethylene)-5,5-dimethylcyclohexen-1-yl)vinyl)-4-morpholinyl coumarin-7-acrylate which is abbreviated as DCICA. The prepared lysosome-targeted Cys near-infrared fluorescent probe has the characteristics of novel structure, lysosome targeting performance and near-infrared fluorescence emission (wherein an emission wavelength is 680 nm), can realize high-selectivity high-sensitivity detection of a Cys content of a solution, conducts specific detection of Cys in cell lysosome by using a laser confocal imaging technology, is of important guiding significance to research on the molecular mechanism of participation of the Cys in the life activity of the lysosome, and has a wide application prospect.

The invention discloses fluorochrome for cytolysosome positioning and a preparation method and application thereof. The preparation method of the fluorochrome compound includes the steps that a benzophenone derivative containing methyl substituents is reacted under the catalysis of Zn / TiC14, an obtained product and N-bromosuccinimide are subjected to a bromination reaction, then a product is reacted with morpholine, and the tetraphenyl ethylene derivative stain containing morpholine groups is obtained. The preparation method is easy to implement, raw materials are easy to get, and reaction conditions are mild. The obtained fluorochrome contains tetraphenyl ethylene fluorescence groups capable of gathering the activity of inducing fluorescence emission and can be used for performing specific staining on all kinds of cytolysosome. The fluorochrome has the advantages of being small in cytotoxicity, stable in cell metabolism resistance, good in photobleaching resisting effect and the like and hardly affects normal physiological activities of cells, and a new method is provided for observing the morphologic changes of cytolysosome for a long time. The fluorochrome can be widely applied to monitoring the morphology of cytolysosome, observing the apoptosis process and the like.

The invention discloses a pH response type lipid based on dendrimers as well as a preparation method and application of the pH response type lipid, and belongs to the field of biological materials. The pH response type lipid disclosed by the invention has different surface charges under different pH environments. The specific forms are that negative electricity, neutrality or micro positive electricity are shown in an in vivo physiological environment to ensure that the pH response type lipid can have good biocompatibility, and amino groups are gradually exposed to expose more positive charges or realize charge reversal by using the pH differences between tumor tissues and normal tissues or between the inside and outside of tumor cells when the pH response type lipid reaches tumor tissue places, so that the contact between a positive electric carrier and a negative electric cell membrane is finished, and then the process of cell endocytosis is promoted. In a cytolysosome, a cationic vector continuously gives play to proton sponge effect or lysosome membrane splitting action so as to escape from lysosome.

The invention discloses a mesoporous silicon dioxide nano particle with a bifluorescence mark, which is a mesoporous silicon dioxide nano particle formed by loading fluorescein isothiocyanate and rhodamine 6G containing a molecular lactam ring together. The invention also discloses a preparation method of the mesoporous silicon dioxide nano particle with the bifluorescence mark and application of the mesoporous silicon dioxide nano particle in detecting a pH value in cell lysosome. The mesoporous silicon dioxide nano particle containing an alkali sensitive FITC (Fluorescein Isothiocyanate) fluorescence molecule and an acid sensitive rhodamine-lactam molecule is used for detecting the pH of the lysosome by a ratio method and has a wide application prospect in the aspect of early diagnosis of diseases, such as cystic fibrosis, asthma, and the like.

The invention relates to the technical field of pH fluorescent probes and particularly relates to a lysosome targeted pH fluorescent probe for monitoring cell autophagy as well as preparation and application of the lysosome targeted pH fluorescent probe. The preparation method comprises the following steps of dissolving 2-(2-aminoethyl)-3',6'-bis(diethylamino) spiro [isoindole-1,9'-xanthan]-3-ketone and 2-(2-methoxyethoxy)4-methyl benzene sulfonic acid ethyl ester in N, N-dimethylformamide, and carrying out heating reflux to obtain a crude product; and removing a solvent from the crude product, and separating through a silica gel column to obtain a pure product. Cytotoxicity tests show that the probe has almost no toxic or side effect on cells, a cell co-localization experiment determinesthat the probe can specifically target a cell lysosome, and a laser confocal microimaging experiment shows that the probe has good cell membrane permeability and can perform high-sensitivity detectionon pH change in the lysosome. The probe provided by the invention can monitor the autophagy process of the cells by detecting the change of pH in the lysosome.

The invention discloses a carbazolyl two-photon fluorescent probe and a preparation method and application thereof. The carbazolyl two-photon fluorescent probe uses carbazole as a matrix and adopts astructural formula as follows: FORMULA. The two-photon fluorescent probe molecule shows specific response and high sensitivity in a system in which cysteine (Cys) coexists with other interfering reagents. Cytotoxicity tests show that the probe has almost no toxic and side effects on cells; in addition, the two-photon confocal fluorescent microscopic imaging experiments show that the fluorescent dye Lyso-DCHO has good permeability to an MCF-7 cell, can effectively position a lysosome in the cell (positioning coefficient is 0.90), and is suitable for visual detection of the Cys in the cytolysosome.

The invention provides a pyrrole-naphthalimide derivative fluorescent probe as well as a preparation method and application thereof. The chemical structural formula of the pyrrole-naphthalimide derivative is shown in the specification; the method comprises the following steps of: dissolving N-morpholineethyl-2, 4-dimethyl-5-formyl pyrrole-3-formamide and 4-hydrazino-N-hydroxyethyl naphthalimide inan organic solvent; dropwise adding acetic acid into the obtained solution to serve as a catalyst, and then carrying out reflux stirring reaction at 80 DEG C for 3-4 hours; and cooling to room temperature, carrying out reduced pressure suction filtration, and washing the obtained solid residue with ethanol to obtain the pyrrole-naphthalimide derivative fluorescent probe. The pyrrole-naphthalimidederivative fluorescent probe disclosed by the invention can selectively react with copper ions under physiological conditions, a red solution is faded, green fluorescence is remarkably enhanced, andthe pyrrole-naphthalimide derivative fluorescent probe as a fluorescent probe is particularly applied to convenient detection of the copper ions in a cytolysosome.

The invention belongs to the technical field of biological medicine, and particularly relates to an iridium complex, the structural general formula of the iridium complex is shown as a following formula I or formula II: wherein R1, R2, R3, R4, R5, R6, R7 and R8 are respectively and independently selected from one of hydrogen, alkoxy and aryl; Y1 and Y2 are ions counteracting the iridium complex main body; n1, n2, m1 and m2 are ionic valences, the absolute value of n1 is equal to the absolute value of n2, and the absolute value of m1 is equal to the absolute value of m2. The iridium complex disclosed by the invention is good in water solubility, can be specifically combined with cytolysosome, can generate singlet oxygen under an illumination condition, has an obvious photodynamic therapy effect on cells, does not generate singlet oxygen under a dark condition, does not have toxicity, and has a wide application prospect in photodynamic therapy drugs.

The invention relates to use of cordyceps cicadae in preparation of drugs for preventing or treating gout. According to the use, due to cordyceps cicada preparation products, a novel gout preventing or treating method is provided and is obvious in effect. The cordyceps cicadae have the functions of reducing blood and urine creatinine, increasing endogenous creatinine clearance rate, increasing the content of serum protein, reducing the discharge of urinary protein, and the like. Therefore, the cordyceps cicadae have definite treatment effect on early- and middle-stage chronic renal insufficiency patients. Confirmed by further researches: the cordyceps cicadae have relatively good treatment effect on renal tubulointerstitial lesions and can be used for protecting Na<+>-K<+>-ATPase of renal tubule cells, alleviating cytolysosome and cell lipid peroxidation injury, improving renal hemodynamics and alleviating endothelial cell injury and blood coagulation property.

The invention relates to a method for targeted detection of H2S in lysoome through carbon quantum dots, and belongs to the technical field of a biosensor and ion recognition. The fluorescence intensity of a synthesized carbon quantum dot CD-dopa-morph fluorescent probe and H2S in a 575 nm position can be obviously enhanced through photoinduced electron transfer. The H2S detection lowest limit of the carbon quantum dot fluorescent probe reaches 70nM. The carbon quantum dot fluorescent probe has the advantages that the synthesis method is simple; the biocompatibility is good; the cell toxicity is low; the detection sensitivity is high; the detection is fast; the signal is stable; the possibility is provided for the realization of clinic detection of H2S in cytolysosome.

The invention provides a copper-terephthalic acid nano particle, and a preparation method and applications thereof. The copper-terephthalic acid nano particle can release Cu<2+> under an acidic condition and can be oxidized by hydroxyl free radicals to generate fluorescent substances. Soluble starch is arranged in the copper-terephthalic acid nano particle and is capable of maintaining a stable Zeta potential of the copper-terephthalic acid nano particle in solutions with different pH values. The nano particle is used as a nano fluorescence imaging probe and can be decomposed in acidic lysosome to release Cu<2+>; and Cu<2+> can further catalyze decomposition of H2O2 in lysosome of cells to generate hydroxyl free radicals. Hydroxyl free radicals can oxidize terephthalic acid of the nano fluorescence imaging probe to obtain hydroxyl terephthalic acid with a fluorescent property, thus the fluorescence imaging strength of the lysosome of cells is obviously higher than the fluorescence imaging strength of other parts of cells, and labeling of lysosome is realized therefore.

The invention discloses a cytolysosome-targeting anticancer cluster and a preparation method thereof. The anticancer cluster is prepared by mixing a small-molecular anticancer drug serving as a ligand with chloroauric acid and radiating a formed mixture with gamma rays. The prepared anticancer cluster is an 8e-structure anti-cancer nanocluster with precise atoms; the number of anti-cancer drugs in the nanocluster is precise, introduction of external lysosome targeting groups is not needed, the anti-cancer drugs can naturally penetrate through cell membranes to be enriched in lysosome, precise chemotherapy drug delivery is conducted, and cancer cells are effectively killed; and therefore, other diseases caused by excessive chemotherapeutic drugs in the body are avoided, and the nano-cluster directly synthesized by the anti-cancer drugs has an application value in realizing targeted quantitative administration and cancer treatment.

The invention discloses a multifunctional lysosome pH probe based on benzimidazole and a preparation method and application thereof. The probe is simple in preparation process, and only 2-methylbenzimidazole and p-dimethylaminobenzaldehyde need to be subjected to a high-temperature tube sealing reaction for 12-24 hours under protection of trimethylchlorosilane; and simple separation and purification on the product is then conducted to obtain the product. The probe has a good ratio type fluorescence characteristic when the pH value is 2.5-7.0, the pKa value is 4.74, and the probe has high targeting property on lysosome, so that the probe is particularly suitable for detecting the pH value of cell lysosome. In addition, the probe also has the advantages of good H<+> selectivity, good light stability, good reversibility, large Stokes shift and the like. When being applied to monitoring of cell activities such as lysosome autophagy, the probe shows good biocompatibility and high-sensitivity real-time in-situ monitoring capability.

The invention provides a morpholine-pyridine-merocyanine derivative fluorescent probe as well as a preparation method and application thereof. The chemical structural formula of a morpholine-pyridine-merocyanine derivative is shown in the specification. The morpholine-pyridine-merocyanine derivative fluorescent probe disclosed by the invention can selectively act with carboxylesterase (CEs) under pure water phase physiological conditions. The fluorescence color of the solution is changed from green to orange yellow, and a typical ratio fluorescence signal is presented. The invention particularly relates to application of the fluorescent probe as a CEs fluorescent probe in cell lysosome fluorescence imaging.

The invention relates to a nano gel containing platinum nano particles and a preparation method and application thereof. The nano gel takes cisplatin as a cross-linking agent in advance, can wrap quinacrine dye, and then reduces the cisplatin in the nano-gel in situ under the reduction of ethanol so as to form the platinum nano particles. Quinacrine is a lysosome dye, and can label lysosomes in cells in combination with the action of the nano gel. By utilizing the superoxide dismutase-like characteristics of the platinum nano particles, in the fluorescence imaging process, the platinum nano particles can remove active oxygen free radicals generated by illumination induction, so that the lysosomes can be protected from being damaged in the imaging process, and the long-term, stable and low-phototoxicity cell lysosome imaging is realized.

The invention provides a pyrrole-merocyanine derivative fluorescent probe, and a preparation method and application thereof. The chemical structural formula of a pyrrole-merocyanine derivative is as shown in the specification. The preparation method comprises the following steps: dissolving N-morpholinoethyl-2,4-dimethyl-5-formylpyrrole-3-formamide and N-ethyl benzothiazole iodate in an organic solvent; dropwise adding piperidine as a catalyst into a solution obtained in the previous step, and then carrying out a reflux stirring reaction at 80 DEG C for 3-4 h; and performing cooling to room temperature, carrying out reduced-pressure suction filtration, cleaning an obtained solid residue with ethanol, and carrying out recrystallizing with ethanol to obtain the pyrrole-merocyanine derivativefluorescent probe. The pyrrole-merocyanine derivative fluorescent probe can selectively react with hypochlorite under pure water phase physiological conditions, allows the yellow color of a solutionto fades while the green fluorescence of the solution to remarkably weaken, and t is particularly applied to convenient detection of hypochlorite in cytolysosome as a fluorescent probe.

The invention provides a morpholine-indanone-chalcone derivative fluorescent probe as well as a preparation method and application thereof. The chemical structural formula of a morpholine-indanone-chalcone derivative is shown in the specification. The preparation method comprises the following steps: dissolving 5-hydroxy-1-indanone, 4-(4-morpholine) benzaldehyde and sodium hydroxide in an organic solvent, carrying out reflux stirring reaction, acidizing with hydrochloric acid until the pH is equal to 6, and treating to obtain an intermediate 5-hydroxy-2-(4-morpholine benzyl subunit)-2, 3-dihydro-1H-indanone; dissolving the chitosan, acetic anhydride and triethylamine in an organic solvent; stirring and reacting at room temperature to obtain the morpholine-indanone-chalcone derivative fluorescent probe. The morpholine-indanone-chalcone derivative fluorescent probe can selectively act with carboxylesterase (CEs) under the condition of 95% of water phase (containing 5% of dimethyl sulfoxide, v / v), green fluorescence is remarkably enhanced, and the morpholine-indanone-chalcone derivative fluorescent probe is particularly applied to cell lysosome fluorescence imaging as a CEs fluorescent probe.

The invention belongs to the technical field of preparation of antitumor drugs and particularly discloses a polypeptide-micelle-type diagnostic reagent AGPR with an aggregation-induced emission (AIE) property and application of the polypeptide-micelle-type diagnostic reagent AGPR in near-infrared-region biological imaging. The diagnostic reagent AGPR is of a spherical polypeptide micelle formed by self-assembly of an amphiphilic micromolecular functional peptide ACBT-GGFLG-PEGn-R8GD in an aqueous solution, wherein n is greater than or equal to 4 and less than or equal to 20. The novel AIEgen compound ACBT designed and synthesized by the invention is a linear D-A-A molecule, an emission peak value of the novel AIEgen compound ACBT is located in a near-infrared region I; and the ACBT molecule is further modified by using a multifunctional chimeric peptide GGFLG-PEG8-R8GD, so that the AIEgen molecule (ACBT) can be efficiently enriched in a tumor region, and the novel AIEgen compound ACBT has obviously enhanced fluorescence intensity in a cytolysosome / endosome rich in Cathepsin B, has an excellent imaging effect, and therefore can be advantageously applied to specific tracing of tumor cells.

The invention provides a chromene pyridine derivative fluorescent probe as well as a preparation method and application thereof. The structural formula of the fluorescent probe is shown in the specification. The specific preparation method comprises the following steps: dissolving 3H-benzo[f]chromene-2-formaldehyde and 4-methyl-1-(2-morpholine-4-ethyl)-pyridine bromide in ethanol, dropwise addingpiperidine as a catalyst, carrying out reflux stirring at 80 DEG C for 4-5 hours, cooling, standing to room temperature, carrying out reduced pressure suction filtration, and cleaning the obtained solid with ethanol to obtain the chromene pyridine derivative fluorescent probe. The chromene pyridine derivative fluorescent probe can selectively react with hypochlorite under pure water phase physiological conditions, the solution is yellow and fades, meanwhile, red fluorescence is remarkably weakened, and the chromene pyridine derivative fluorescent probe is particularly applied to convenient detection of hypochlorite in cytolysosome as a fluorescent probe. The probe does not need any organic solvent for hydrotropy in a working environment, is very beneficial to being applied to a biologicalsystem, and has wide potential application value.

The invention provides a pyrrole dihydrazone derivative fluorescent probe as well as a preparation method and an application thereof. The chemical structural formula of a pyrrole dihydrazone derivative is shown in the specification; the preparation method comprises the steps: dissolving N-morpholinoethyl-2,4-dimethyl-5-formylpyrrole-3-formamide and hydrazine hydrate into an organic solvent; dropwise adding acetic acid as a catalyst into the obtained solution, and then carrying out reflux stirring reaction at the temperature of 80 DEG C for 3-4 h; and cooling the obtained solution to room temperature, carrying out reduced pressure suction filtration, and cleaning the obtained solid residue with ethanol to obtain the pyrrole dihydrazone derivative fluorescent probe. The pyrrole dihydrazone derivative fluorescent probe can selectively react with mercury ions under physiological conditions, the solution is changed from colorless to green, meanwhile, blue fluorescence is remarkably enhanced, and the pyrrole dihydrazone derivative fluorescent probe as a fluorescent probe is particularly applied to convenient detection of mercury ions in cytolysosome.

The invention provides a rhodamine-sialic acid conjugate and a synthesizing method and application thereof to lysosome imaging, and relates to the rhodamine-sialic acid conjugate. In the rhodamine-sialic acid conjugate, a connecting arm connected between rhodamine and sialic acid adopts an amido bond or other structures. The rhodamine-sialic acid conjugate is prepared through the steps of adding 9-amino sialic acid and N-hydroxysuccinimide rhodamine X-5 carboxylic acid ester to a mixed solution of dioxane and water, adjusting pH to 9 through a saturated sodium carbonate solution, performing areaction for a night, removing a solvent of a reaction system, and performing HPLC separation to obtain the rhodamine-sialic acid conjugate. Living cell lysosomes are accurately positioned, and the signal-noise ratio is high; red fluorescence is launched in the lysosomes, the acidity of the lysosomes is changed, and a probe maintains hyperfluorescence; retention in the lysosomes is independent ofthe acidity of the lysosomes; real-time fluorescence imaging is performed on the lysosomes; and the rhodamine-sialic acid conjugate disclosed by the invention is used for the lysosomes to perform random restructured fluorescence microscopic imaging of ultrahigh resolution.

The invention relates to a pyrrole-rhodamine acylhydrazone derivative as well as a preparation method and application of the derivative, belonging to the organic synthesis field. The preparation method of the pyrrole-rhodamine acylhydrazone derivative comprises the following steps: (S1) adding N-(2-morpholin-4-ethyl)-5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxamide into an organic solvent, and adding rhodamine 6G hydrazide, so as to obtain a mixture; (S2) carrying out reflux stirring reaction on the mixture obtained in the step (S1) at a normal pressure; (S3) after the reaction is finished, cooling to the room temperature so as to separate solids, carrying out reduced pressure filtration, and extracting filter residue; and (S4) washing the filter residue obtained in the step (S3), so as to obtain the pyrrole-rhodamine acylhydrazone derivative. The pyrrole-rhodamine acylhydrazone derivative is capable of selectively acting with bivalent copper ions, blue fluorescence is changed into greenfluorescence, a ratio fluorescence effect is realized, the naked eye distinguishing detection can be realized, and particularly, the pyrrole-rhodamine acylhydrazone derivative can be taken as a fluorescence probe to be applied to the convenient detection of bivalent copper ions in cell lyase.

The invention discloses a lysosome fluorescent probe of chalcone as well as a preparation method and application of the lysosome fluorescent probe, and belongs to the technical field of organic molecular fluorescent probes. The preparation method comprises the following steps: adding 2 '-hydroxychalcone HCA and 1, 3-dibromopropane into an organic solvent for reaction, carrying out silica gel column chromatography separation to obtain an intermediate Br-HCA, adding the intermediate Br-HCA and morpholine into the organic solvent for reaction, and carrying out silica gel column chromatography separation to obtain the lysosome fluorescent probe Lyso-HCA. The preparation method of the fluorescent probe is simple, rapid and low in cost, the prepared fluorescent probe is low in background interference, high in detection sensitivity and high in excitation capacity when being applied to cell fluorescence imaging, and the fluorescent probe is good in stability to an acid-base environment and good in specificity to lysosome fluorescence imaging. The probe provides a tool with a wide application prospect for cell lysosome fluorescence imaging research.

The invention discloses application of a near-infrared light-emitting binuclear ruthenium (II) complex as a tumor cell (HeLa) recognition probe and a lysosome positioning probe. The fluorescence intensity of the complex in tumor cells is obviously higher than that of normal cells (HEK), and recognition of the tumor cells can be achieved. Besides, after entering cells, the complex is positioned intumor cell lysosome in a targeted manner, almost no cytotoxicity exists under an imaging concentration condition, and long-time real-time fluorescence monitoring of the cell lysosome can be achieved.The complex has great development potential as a tumor cell imaging reagent.