90 results about "Mitochondria targeted" patented technology

The present invention relates to compositions and methods for providing mitochondria-selective targeting agents covalently linked to desired cargo such as radical scavenging agents. Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using specific structural signaling features recognizable by cells as mitochondrial targeting sequences are discussed. A method for delivering these agents effectively into cells and mitochondria where they act as electron scavengers by way of certain targeting sequences is also disclosed. Mitochondria and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels. In further preferred embodiments, the composition for scavenging radicals in a mitochondrial membrane includes a radical scavenging agent and a membrane active compound having a high affinity with said mitochondrial membrane and associated methods. In another embodiment, the cargo transported by mitochondrial-selective targeting agents may include an inhibitor of nitrous oxide system (NOS) enzyme activity.

Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using specific structural signaling features recognizable by cells as mitochondrial targeting sequences are discussed. A method for delivering these agents effectively into cells and mitochondria where they act as electron scavengers by way of certain targeting sequences is also disclosed. Mitochondria dysfunction and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels.

The present invention relates to a pharmaceutical or veterinary or nutritional or personal care composition comprising coenzyme Q₁₀ (CoQ₁₀), reduced CoQ₁₀, or mixtures thereof and oxygenated dibenzo-α-pyrone or an amino acyl ester thereof. The composition of the present invention is able to support and/or provide therapy to individuals at risk and/or under treatment for dysfunctions of energy metabolism, and specifically, for mitochondrial diseases.

The present subject matter relates to red emitting mitochondria-targeted aggregation induced emission (AIE) probes as an indicator for membrane potential and mouse sperm activity. The present subjectmatter relates to AIE-active fluorescent probes for reactive oxygen species (ROS) detection and related biological applications, such as inflammation imaging and glucose assay, as well as the preparation and application of red fluorescent AIEgens.

The invention discloses a mitochondria-target fluorescent carbon dot as well as a preparation method and application thereof. The fluorescent carbon dot is mainly prepared from the following raw materials in parts by weight: 1-20 parts of chitosan, 1-10 parts of ethylenediamine and 1-10 parts of mercaptobutanedioic acid; and the carbon dot with excellent fluorescence property is prepared from the chitosan, the ethylenediamine and the mercaptobutanedioic acid as raw materials through a hydrothermal method in one step. Compared with the prior art, the carbon dot is capable of achieving fast, no-clean and long-term photostable (anti-bleaching) imaging on mammalian cell mitochondria, and can be used for directionally conveying an anti-tumor drug to the mitochondria as a carrier, thereby achieving mitochondria-based targeted cancer therapy. In addition, the carbon dot also has the advantages of low preparation cost, good water dispersibility and low cytotoxicity, and hopefully replaces a commercial mitochondria fluorescent probe widely used at present.

The invention provides a mitochondria-targeting micelle drug delivery system capable of reversing drug resistance of tumor. The drug delivery system is a polymer micelle which is obtained through self assembly of a block copolymer folic acid-polyethylene glycol-polyaspartic acid, also a mitochondria-targeting doxorubicin-triphenylphosphine compound (TPP-DOX) is synthesized, and doxorubicin and doxorubicin-triphenylphosphine (DOX/TPP-DOX) are together wrapped in the polymer micelle, so that the drug delivery micelle is obtained. The drug delivery system is capable of giving play to active targeting effect and possesses acid-sensitive characteristic, is capable of simultaneously releasing doxorubicin in mitochondria and nucleus in a positioning way after entering a tumor cell, helps to enhance antitumor activity and reverse the drug resistance of tumor, and provides a new strategy for the dilemma that chemotherapeutics drugs easily generate drug resistance.

The invention discloses a mitochondria target hydrogen peroxide molecular fluorescent probe and a preparation method and application thereof and belongs to the technical field of analytical chemistry. A molecular structural formula of the probe is shown as the formula I and is short as Mito-H2O2. The preparation method of the probe molecule is simple, achieves quick detection on hydrogen peroxide molecules, is good in selectivity and strong in antijamming capability, can be used for detecting hydrogen peroxide molecules in mitochondria of cells, has the characteristics of being quick, simple and flexible and has wide application prospect in the biological molecular detection field.

The invention discloses a double-targeting polypeptide-antibody-drug conjugate, and a prepared method and antineoplastic application thereof. The double-targeting polypeptide-antibody-drug conjugate structurally includes four components of (A), tumor specificity targeting polypeptide; (B), an antineoplastic drug; (C), a mitochondria target functional group; and (D), hydrazone bonds used for connecting the polypeptide and the antineoplastic drug. The tumor specificity targeting polypeptide is connected with the antineoplastic drug by a connecting arm comprising the hydrazone bonds; the antineoplastic drug is connected with the mitochondria target functional group by chemical bonds; and the tumor specificity targeting polypeptide is suitable for targeting the conjugate to a tumour cell and marker protein LAPTM4B carried on the surface of the tumour cell is used as a specificity target. A molecular target is combined with an organelle target, selective uptake of the drug in the tumour cell can be increased, an acting site of a DOX drug can be transferred form cell nucleus to mitochondria, and therefore the condition that the tumour cell is killed by drug resistance is avoided.

The invention relates to the field of compound detection, in particular to a method for screening mitochondria targeted compounds by using zebra fish. The method mainly comprises the following steps of: zebra fish selection, compound treatment, dyeing treatment and quantitative/qualitative analysis, wherein the dyeing treatment is that the dyeing treatment is performed on the zebra fish, on whichthe compound treatment is performed, for 0.5 to 1 hour at the temperature of 28 DEG C by taking JC-1 or DASPEI as a staining agent. The method covers the shortage that mitochondrial damage cannot be detected in vivo in the prior art by using an in vivo experimental analysis method for screening the mitochondria targeted compounds by using the zebra fish, is convenient, swift, economic and practical, and has the characteristics of high flux and high specificity.

The invention belongs to the technical field of organic chemistry and discloses a conjugated chain functional benzoindole hematocyanine dye and an application. The stability of the novel hematocyaninedye is obviously superior to that of an existing cyanine fluorescent probe, and the novel hematocyanine dye has the multiple functional activity such as near infrared fluorescence and tumor mitochondria targeted accumulation and photo-thermal and photo-power synergic treatment of killing tumor cells. Applied as the near infrared fluorescence probe in living cell imaging research and living body infrared optical molecular imaging, a precise and efficient photo-thermal and photo-power antitumor effect is achieved synchronously. The dye can be applied to near infrared in vivo optical imaging andphoto-sound imaging of tumors, is applied to optical assisted operation navigation, and has an efficient antitumor function. The dye not only can develop a target tissue in real time, but also kill tumor cells specifically. The preparation method of the benzoindole hematocyanine dye is mild in reaction condition, simple in step and easy to operate and low in raw material cost, and is easy to purify and relatively high in yield.

Mitochondriotropic phospholipid vesicles, i.e., mitochondriotropic liposomes, that comprise a hydrophobized amphiphilic delocalized cation, such as those comprising, e.g., a triphenylphosphonium or a quinolinium moiety, incorporated into the phospholipid membrane of the vesicles, or liposomes, are disclosed. The hydrophobized portion of the amphiphilic delocalized cation, e.g., a fatty acid or other phospholipid derivative, is embedded in the phospholipid membrane of the liposome, and the amphiphilic portion of the cation is exposed on the surface of the liposome. Mitochondriotropic liposomes constitute a mitochondria-targeted drug delivery system, permitting the transport of a high payload of therapeutic water-soluble molecules in their native (i.e., active) state specifically and exclusively to mitochondria in living mammalian cells.

The invention discloses a mitochondria target fluorescence probe, as well as a preparation method and application thereof. The probe has a structure as shown in formula (I). The mitochondria target fluorescence probe can overcome the defects of the traditional commodity probe and has the advantages of high fluorescence quantum yield, excellent water solubility, less influences of environment property and acid-base property on the probe, good imaging effect of mitochondria, low toxicity, high photo-bleaching resistance, and the like, so that the mitochondria target fluorescence probe has excellent application prospects in the fields of long-time living cell mitochondria imaging and bio-labeling.

The invention discloses hyaluronic acid modified mitochondria target liposome and a preparation method thereof. The mitochondria target liposome disclosed by the invention is prepared from drug carrying liposome and outer-layer modifying hyaluronic acid, wherein the drug loading liposome is liposome covered by hydrophobic drug and dequalinium chloride, and the hydrophobic drug is any one chosen from adriamycin, taxol, 10-hydroxycamptothecine, irinotecan or cis-platinum. The hyaluronic acid modified mitochondria target liposome disclosed by the invention has the beneficial effects that receptors are effectively targeted, uptake of tumor cells to liposome is improved, cell mitochondria is further targeted in the tumor cells, a function of damaging the mitochondria is achieved, tumor cell apoptosis is promoted, tumor cell growth is inhibited, and ability of overcoming multidrug resistance of the tumor cells is achieved.

A mitochondria targeted gold nanoparticle (T-3-BP-AuNP) decorated with 3-bromopyruvate (3-BP) and delocalized lipophilic triphenylphosphonium (TPP) cations to target the mitochondrial membrane potential (Δψm) was developed for delivery of 3-BP to cancer cell mitochondria by taking advantage of higher Δψm in cancer cell compared to normal cells. This construct showed remarkable anticancer activity in prostate cancer cells compared to non-targeted construct NT-3-BP-AuNP and free 3-BP. Anticancer activity of T-3-BP-AuNP was further enhanced upon laser irradiation by exciting the surface plasmon resonance band of AuNP and thereby utilizing a combination of 3-BP chemotherapeutic and AuNP photothermal effects. T-3-BP-AuNPs showed markedly enhanced ability to alter cancer cell metabolism by inhibiting glycolysis and demolishing mitochondrial oxidative phosphorylation in prostate cancer cells. Our findings demonstrated that mitochondria targeted and concerted chemo-photothermal treatment of glycolytic cancer cells with a single NP may have promise as a new anticancer therapy.

The present invention relates to a mitochondria targeting peptide, a fusion protein in which the peptide is bound to the carboxyl terminus of a protein transduction domain, a fusion protein in which the peptide is bound to the carboxyl terminus of a protein transduction domain and an antioxidant is bound to the carboxyl terminus of the peptide, an antioxidant composition and a composition for preventing or treating Parkinson's disease including the fusion protein in which the antioxidant is bound, a recombinant polynucleotide in which a polynucleotide coding a protein transduction domain, a polynucleotide coding the peptide, and a polynucleotide coding an antioxidant protein are sequentially bound, to an expression vector including the polynucleotide, and to a transformed host cell including the expression vector.

The mitochondria targeting peptide according to the present invention targets mitochondria with high efficiency not only when the peptide exists alone but also when the peptide is bound to a protein transduction domain and/or to an antioxidant. Further, the peptide has a small size and is thus a very suitable targeting carrier. The peptide becomes processed when introduced into mitochondria, and thus stably delivers the drug carried by the peptide.

The invention discloses an application of a heptamethine indocyanine organic dye as a mitochondria fluorescent probe. The structural formula of the heptamethine indocyanine organic dye is as follows: the formula is as shown in the specification. The fluorescent probe has excellent mitochondria targeting capacity, and is capable of emitting red fluorescence of which the reflection wavelength is 610nm after being combined with mitochondria. Meanwhile, the probe also has the advantages of being high in fluorescence quantum yield, long in imaging time, high in signal-noise ratio and low in cytotoxicity, and can be used as a novel mitochondria imaging reagent.

The invention discloses a preparation method and an application of a mitochondria-targeted double-signal turn-on formaldehyde fluorescent nano-probe. The formaldehyde fluorescent nano-probe is based on both fluorescent resonance energy transfer and self-assembly effect. The nano-probe hardly has fluorescence in water; when the nano-probe is reacted with formaldehyde, two free fluorescent compounds are generated, thus achieving double-turn-on effect and further improving the accuracy of a detection result. The nano-probe has excellent specificity on the formaldehyde. A confocal fluorescence microscope test proves that the nano-probe can permeate through a cell membrane and enters mitochondria in a cell, and can detect the change of concentration of formaldehyde in the cell. The nano-probe is a novel tool for researching the metabolic mechanism of the formaldehyde in mitochondria and has great prospect in the field of biology.

A low-power white-light-driven mitochondrial-targeting fluorescent probe photosensitizer as well as a synthesis method and application thereof are disclosed. The molecular formula of the photosensitizer is shown in the description, and is short for AIE-FR-TPP. The photosensitizer has the advantages that the photosensitizer has aggregation-induced luminescence characteristics and zebrafish mitochondrial targeting characteristics, generates reactive oxygen for photodynamic therapy under low-power white light irradiation, and can monitor the morphological changes of zebrafish mitochondria on reactive oxygen species damage in real time, and is taken as a favorable research tool for real-time monitoring of zebrafish mitochondrial fluorescence imaging and photodynamic therapy. The probe photosensitizer not only has zebrafish mitochondria specific imaging capabilities and photodynamic therapy properties, but also can monitor mitochondrial reactive oxygen species damage in situ in real time.

The invention discloses application of an iridium complex in preparing mitochondria targeted anti-tumor drugs. The structural formula of the iridium complex is [Ir(ppy)2(HPIP)]C1, wherein ligand represented by ppy is 2-phenylpyridine, ligand represented by HPIP is 3-(1H-imidazole[4,5-f][1,10]phenanthroline-2-yl)phenol. The iridium complex has the high inhibiting effect on human tumor cells HeLa, HepG2, A-549 and a cisplatin resistant strain CP/R-A549, mitochondria in tumor cells can be stored up, tumor cell apoptosiss can be induced, and the iridium complex can serve as the new anti-tumor drugtaking tumor cell mitochondria as target sites.

The invention discloses a method for preparing a mitochondria targeted spinning scavenger MitoPBNs (spinning probe). The structural formula of the MitoPBN is shown in a formula (I). A synthesis flow is shown in the formula (II), and comprises the following steps of: performing elimination reaction on 4-hydroxybenzaldehyde and dibromo-straight-chain paraffin under alkali condition to prepare a compound 3; reacting the compound 3 with triphenylphosphine to prepare the compound 4; in ethanol, mixing the compound 4, 2-nitro-2-methylpropane, a 4A molecular sieve and zinc powder in a solvent, adding dropwise a glacial acetic acid, stirring and reacting the mixed solution at room temperature, placing the mixed solution in a refrigerator for refrigeration, and performing separation and purification to prepare the spinning probe MitoPBN; and performing liposome packing treatment. The method has the characteristics of relatively fewer synthesis steps, low raw material cost, readily available raw materials and relatively higher product purity. The probe for scavenging free radical signals can enter cell mitochondria.

The invention discloses a preparation method and application of a mitochondria-targeted dihydropyridine compound. The mitochondria-targeted dihydropyridine compound has structures of a formula (I) and a formula (II) (shown in the description). Experiments prove that the mitochondria-targeted dihydropyridine compound is capable of effectively eliminating reactive oxygen species (ROS) generated by ionization radiation and therefore can be applied to the treatment of free radical-induced relevant diseases such as Alzheimer's disease and ionization damage disease. The preparation method is simple, and the product is easily prepared and pollution-free.

The invention discloses a viscosity fluorescent probe with a mitochondrial targeting function as well as a preparation method and application thereof. The structural formula of the fluorescent probe is shown in the specification. The preparation method comprises the following steps: dissolving 5-methyl-3-(2'-benzothiazolyl)-4-hydroxybenzaldehyde and 2-pyridylacetonitrile onium iodide into absoluteethyl alcohol, adding piperidine, heating and refluxing the mixture for 6 hours, cooling, filtering, precipitating, and recrystallizing the solid with ethanol to obtain a yellow solid, namely the probe (Z)-2-(2-(3-(2-benzothiazolyl)-4-hydroxy-5-methylphenyl)-1-cyanovinyl)-1-methylpyridine-1-iodide. The fluorescent probe has the advantages of excellent viscosity detection performance, excellent anti-interference capability and good mitochondria targeting positioning function, can be used for monitoring the viscosity change of mitochondria, cells, animal tissues and organs and mouse living bodies, and has a wide application prospect in the field of organism viscosity detection.