98 results about "Mitochondrial targeting" patented technology

The invention relates to the technical field of pharmaceutical preparations, and discloses a composition with liver protection and antioxidation effects and a preparation method thereof.The composition is prepared from galactosamine modified astragalus membranaceus exosome, schisandra chinensis nanocrystals, liquorice-chitosan nanoparticles, lactobacillus acidophilus freeze-dried powder, beta-(1, 3) / (1, 3, 4-tetramethyl-1, 3-pentanediol monoisobutyrate) sourced from saccharomyces cerevisiae, and beta-(1, 3, 4-tetramethyl-1, 3-pentanediol monoisobutyrate). And (6) a dextran, grape exosome-curcumin hybrid vesicle freeze-dried powder, a curcumin-mitochondrial targeting peptide compound, a resveratrol-hydroxypropyl-beta-cyclodextrin inclusion compound and reduced panthenol. According to the liver-protecting and anti-oxidation composition disclosed by the invention, multi-dimensional intervention on liver protection is realized through an elaborately designed ternary system. The system is composed of a traditional Chinese medicine extract, a microorganism-plant exosome combination and a high-bioavailability antioxidant, all the parts have a synergistic effect, and the liver protection effect is remarkably improved.

The invention relates to the technical field of biomedical materials, in particular to an alendronate-modified ZIF-8 encapsulated TPP-carbon dot bone targeting nano-material and a preparation method and application thereof.The alendronate-modified ZIF-8 serves as a carrier, TPP-modified carbon dots are encapsulated in the carrier, citric acid, urea and cerium salt serve as raw materials of the TPP-modified carbon dots, and the alendronate-modified ZIF-8 encapsulated TPP-carbon dot bone targeting nano-material is prepared through a one-step method. After cerium-doped carbon quantum dots are synthesized through a hydrothermal method, TPP is grafted through an amide method, alendronate endows the material with a bone targeting function, and TPP modified carbon dots endow the material with antioxidant and mitochondrial targeting functions. According to the invention, the bone targeting property is excellent, and bone focuses are efficiently enriched; the anti-oxidation and anti-inflammatory capacities are high, and the infected microenvironment can be improved; zIF-8 packaging is stable, and functional components can be controllably released; multiple components cooperate to promote bone repair, accumulation of non-target organs is little, and the composition is safe, reliable and suitable for treatment of various bone-related diseases.

The invention discloses a self-assembled PROTAC nano material based on natural product mitochondria targeting, which is a nano particle prepared from mitochondria targeting molecules, a photosensitizer and PROTAC as raw materials through a nano precipitation method. The mitochondrial targeting molecule is berberine, the photosensitizer is hypericin, and the PROTAC is dBET57; the ratio of the amount of substance of the dBET57 to the amount of substance of the berberine is (1-10): (1-10), and the ratio of the amount of substance of the dBET57 to the amount of substance of the hypericin is (1-10): (1-10). The nano material can be used for blocking multiple energy metabolism pathways of tumor cells, including glycolysis and oxidative phosphorylation, meanwhile, mitochondria is damaged, ferroptosis is induced, and the anti-tumor capacity of pharmacodynamic molecules is improved; bRD4 in tumor cells and downstream carcinogenic protein c-Myc of the BRD4 can be efficiently degraded. The invention also discloses an application of the nano material in preparation of antitumor drugs.

The invention discloses a mitochondrial targeting and apoptosis-inducing photosensitive iridium complex and a preparation method thereof, and particularly discloses a 2, 2 '-bipyridine compound, a cyclometalated iridium complex using the compound as a ligand, a preparation method and application of the 2, 2'-bipyridine compound as an antitumor drug. The cyclometalated iridium complex provided by the invention takes a 2, 2 '-bipyridine compound as a ligand, can selectively induce tumor cell apoptosis under an illumination condition, can be used for preparing antitumor drugs, and has a great potential value in the field of photodynamic treatment of tumors.

The application discloses a green preparation method of a medium-chain acylated hydroxytyrosol lipoid-triphenylphosphine derivative and application of the derivative in mitochondrial-targeted antioxidation, and relates to the following steps: taking hydroxytyrosol and saturated halogenated fatty acids with medium-chain length C8-C12 as raw materials, and synthesizing a medium-chain hydroxytyrosol lipoid compound through a low-field ultrasonic coupling immobilized lipase synergistic directional alcohol hydroxyl acylation reaction; and further synthesizing the lipoid compound through high-speed stirring reaction with a triphenylphosphine compound to obtain a medium-chain acylated hydroxytyrosol lipoid-triphenylphosphine derivative. The derivative has the antioxidation effect of mitochondrial-targeted enrichment and active oxygen radical scavenging. The hydroxytyrosol derivative prepared by the application has the characteristics of green efficiency, directional bonding and simple operation. The acylation reaction of hydroxytyrosol does not need to involve flammable and explosive, easily oxidized and corrosive concentrated sulfuric acid and concentrated nitric acid, and the medium-chain acylated hydroxytyrosol lipoid-triphenylphosphine derivative has mitochondrial targeting, can be used as a potential mitochondrial nutritional supplement product, and has a wide application prospect in the health care functions of anti-aging, cardiovascular protection, diabetes prevention and the like.

The invention relates to the technical field of bone regeneration bioactive components, in particular to a monatomic nano-enzyme targeting mitochondria and accelerating bone regeneration and a preparation method thereof.The monatomic nano-enzyme comprises Fe / Cu monatomic double active sites, triphenylphosphine (TPP) molecules targeting the mitochondria and a porous nano-carrier, and the porous nano-carrier is a dendritic mesoporous silica nano-particle (DMSN). The invention effectively overcomes the defects of poor repair effect and long repair period caused by insufficient mitochondrial targeting, low catalytic efficiency and single function in the existing bone regeneration technology.

This invention relates to the field of bionanomaterials technology, and particularly to mitochondrial-targeting nanomaterials capable of releasing HNO, their preparation methods, and applications. The preparation method of the mitochondrial-targeting nanomaterials capable of releasing HNO includes the following steps: synthesis of a silanized HNO donor: hydroxylamine hydrochloride is dissolved in a mixed solvent of anhydrous tetrahydrofuran and anhydrous pyridine, and a dichloromethane solution of 2-(4-chlorosulfonylphenyl)ethyltrimethoxysilane is added. The mixture is stirred at room temperature, and after post-treatment, a silanized HNO donor is obtained; synthesis of aminated carbon dots: chitosan, ethylenediamine, and mercaptosuccinic acid are dispersed in deionized water, and concentrated hydrochloric acid is added and stirred until dissolved. This preparation method can prepare mitochondrial-targeting nanomaterials capable of releasing HNO, achieving precise delivery, controlled release, and visual tracking of HNO to cardiac mitochondria, solving the technical problems of traditional HNO donors' inability to achieve stable loading on carriers and lack of mitochondrial targeting ability.

The present invention discloses a dual-targeted macrophage membrane nanosystem, its preparation method and application, which belongs to the field of biomedicine. MKA is formed by connecting AuNPs with the mitochondrial targeting peptide KLA and then encapsulating it in the macrophage membrane. During preparation, AuNPs are first synthesized and modified, and then encapsulated with the macrophage membrane. During treatment, it can dual-target tumor cells and mitochondria, enhance radiation-induced DNA damage, inhibit DDR, activate immune pathways, promote T cell infiltration, and consume glutathione and amplify oxidative stress to enhance immune effects. The dose enhancement ratio synergistic with 8GyX-rays is 3.1. In addition, MKA has good biocompatibility in the body, a long blood circulation time, high tumor targeting, and can be quickly cleared through the kidneys. This invention provides a new approach for tumor radioimmunotherapy and helps promote progress in clinical tumor treatment.

The present invention relates to base editing of mitochondrial DNA. More specifically, the present invention relates to: a method for editing mitochondrial DNA bases by using a mitochondrial targeting sequence (MTS); and a base editing system used in the method. The base editing system comprises a DNA binding protein and a deaminase, or polynucleotides encoding these, and does not include an affinity tag or a polynucleotide encoding same. The present invention is useful for editing mitochondrial DNA bases of animal cells or plant cells.

This application discloses a preparation method and application of injectable hydrogel microspheres. By integrating the hydrogel drug delivery system with liposome microparticles obtained by microfluidic technology, NMN is encapsulated by liposome material, and the mitochondrial targeting peptide SS-31 is introduced into the liposome to achieve a more sustained and stable release, thereby enabling NMN to selectively target cell mitochondria and improve the application effect.

The invention belongs to the technical field of biological medicine, and discloses a mitochondrial targeting fluorescent probe and a preparation method and application thereof.The mitochondrial targeting fluorescent probe has the structural general formula shown in the formula (I), and the preparation method comprises the step that in the presence of a basic catalyst, the mitochondrial targeting fluorescent probe is prepared. And carrying out Knoevenagel condensation reaction on the nitrogen-containing heterocyclic ring onium iodide and 4-(di (2-chloroethyl) amino)-2-fluorobenzaldehyde, thereby obtaining the compound. The mitochondrial targeting fluorescent probe has mitochondrial targeting, fluorescence imaging capability and antitumor activity, can be used for preparation of tumor cell mitochondrial imaging reagents and antitumor drugs, provides a new strategy for tumor diagnosis and treatment, and has a good application prospect.

The invention discloses a fluorescent probe for high-sensitivity monitoring of cell mitochondrial autophagy as well as a preparation method and application thereof. The structure of the fluorescent probe is as shown in formula I in the specification. According to the fluorescent probe provided by the invention, a phenol group is used as an electron donor and a pH response unit, hydroxyl tricyanopyrrole is used as an electron acceptor, triphenylphosphine is used as a mitochondrial targeting group, fluorine atoms are introduced to a benzene ring to improve the response rate and the fluorescence intensity, and meanwhile, a thiophene ring is introduced to further expand the fluorescence emission wavelength. The probe can rapidly target mitochondria and emit corresponding fluorescence signals based on pH differences of different autophagy stages, so that real-time, high-sensitivity and high-selectivity monitoring of the mitochondria autophagy process is realized. In addition, the fluorescent probe is simple in molecular structure, small in molecular weight and easy to synthesize, purify and subsequently modify. Cell experiment results show that the probe can accurately trace the mitochondrial autophagy process in cells, and has good application potential in the field of biological imaging and detection.

The invention discloses a mitochondrial targeting pyridinium cyanine photosensitizer compound, a preparation method, a compound and application thereof, and the pyridinium cyanine photosensitizer compound is generated through organic reaction by taking N-methyl-N-hydroxyethyl naphthylamine as an electron donor, pyridinium cyanine as an electron acceptor and double bonds as pi bridge connection. After the pyridycyanine photosensitizer compound is self-assembled and combined with HSA, specific fluorescent staining of mitochondria is achieved, active oxygen is efficiently generated under white light irradiation and directly acts on the mitochondria, and the cancer cell killing efficiency is improved. The preparation method is simple and efficient, and the prepared photosensitizer compound has a good photodynamic therapy effect and biological safety and has a good application prospect.

The invention belongs to the field of fluorescent dyes and biological imaging, and particularly provides a mitochondrial targeting fluorescent dye as well as synthesis and application thereof. The structural formula of the mitochondrial targeting fluorescent dye is shown as a formula (I). The compound is synthesized by one-step heating reaction of benzothiazole-2-acetonitrile and Fisher's aldehyde under the action of alkali. The mitochondrial targeting fluorescent dye has good cell membrane penetrability, can be rapidly taken by cells, and is good in mitochondrial targeting, high in light stability and low in toxicity to the cells. Meanwhile, the preparation process is simple, the cost is low, clear and long-time fluorescence imaging analysis and dynamic fluorescence monitoring on mitochondria in cells can be realized, and the fluorescent probe has a good application prospect.

The invention relates to a covalent mitochondrial fluorescent probe as well as a preparation method and application thereof, the covalent fluorescent probe takes Cy3 or Cy5 with low phototoxicity as a fluorophore and chloroacetyl chloride as a covalent group, the Cy3 or Cy5 is also used as a mitochondrial targeting group, and the chloroacetyl chloride is used as a covalent group. The covalent group chloroacetyl chloride on the fluorescent probe molecule is covalently bound with the mitochondrial inner membrane protein to realize targeted covalent labeling, and compared with other fluorescent probes synthesized by covalent groups, the covalent fluorescent probe has more excellent labeling stability, has good labeling stability, strong light stability and low phototoxicity, and can be used for detecting the mitochondrial inner membrane protein of the mitochondrial inner membrane protein of the mitochondrial inner membrane protein of the mitochondrial inner membrane protein. And the requirements of multicolor imaging and long-term dynamic imaging of mitochondria can be met.

This invention relates to the field of optical sensing and imaging detection technology, specifically to a triphenylene-oxanthracene derivative, its preparation method, and a fluorescent probe for viscosity detection. The triphenylene-oxanthracene derivative has the general formula shown in Formula I. Compared to Rhodamine B, the synthesized triphenylene-oxanthracene derivative exhibits a larger Stokes shift. Furthermore, the fluorescence intensity of the triphenylene-oxanthracene derivative increases with increasing cell viscosity. In addition, the triphenylene-oxanthracene derivative can be further used to detect mitochondrial viscosity, exhibiting good mitochondrial targeting. In summary, the probe improves the Stokes shift, has a wide optical response pH range, and possesses excellent mitochondrial targeting.

This invention discloses a near-infrared fluorescent probe for the rapid and sensitive detection of biothiols (Cys / Hcy) with a large Stokes shift targeting mitochondria. The structural formula of the fluorescent probe is shown in Formula (I). The probe of this invention not only exhibits rapid response time, high sensitivity, and selectivity to cysteine / homocysteine, but also a near-infrared emission response with a large Stokes shift (approximately 200 nm). Furthermore, this probe possesses good cell permeability and mitochondrial targeting ability, making it highly suitable for imaging and detection of Cys / Hcy in live cells.

A naphthaleneimide compound, its preparation method, and application. The present invention provides a naphthaleneimide compound, the structure of which is shown in Formula I: R is selected from one of the following: The present invention also provides a method for preparing the naphthaleneimide compound. The compound has the ability to accurately trace mitochondrial autophagy and has the ability to release peroxynitrite (ONOO) ‑ The responsiveness and mitochondrial targeting capabilities of the ELISA can be applied to prepare a kit for tracking oxidative stress-induced mitophagy and / or peroxynitrite activation.

To provide novel therapeutic compounds that target and inhibit a mitochondrial function, and may serve as anti-cancer therapeutics.SOLUTION: Alkyl-triphenylphosphonium compounds having a saturated, linear alkyl chain of about 9 to about 18 carbons may be used as therapeutic agents to treat cancer. Demonstrative compound dodecyl-TPP (d-TPP) dose-dependently inhibits the propagation of breast cancer stem cells and targets the bulk of the adherent of cancer cells, by decreasing MCF-7 cell viability. Further, d-TPP potently inhibits a mitochondrial oxygen consumption rate, while simultaneously shifting cell metabolism toward a glycolytic pathway. This shift to a strict metabolic dependency on glycolysis may be used to eradicate the residual glycolytic CSC population, by using additional metabolic stressors. For example, d-TPP may be combined with a glycolytic inhibitor or an OXPHOS inhibitor, through co-administration or sequential administration, to treat cancer and eradicate CSCs.SELECTED DRAWING: Figure 2

The present invention provides a hydrogenation-responsive coenzyme NAD(P)H fluorescent probe, a preparation method, a fluorescent sensor and an application, and belongs to the technical field of fluorescent probes. In the presence of NAD(P)H, the trimethylbenzoquinone functional group in the molecule of the hydrogenation-responsive coenzyme NAD(P)H fluorescent probe prepared by the present invention can be catalytically reduced to a responsive trimethylhydroquinone by an organic metal iridium or organic metal rhodium catalyst. The generated trimethylhydroquinone will rapidly undergo intramolecular cyclization and fall off from the probe molecule, turning on the fluorescence of the probe molecule, thereby achieving a rapid and efficient fluorescent response to NAD(P)H. The hydrogenation-responsive coenzyme NAD(P)H fluorescent probe of the present invention has a stable structure, high fluorescence quantum yield, a wide pH adaptability range, good biocompatibility, and mitochondrial targeting. When combined with highly active organic iridium and rhodium catalysts, it can quickly, sensitively and specifically detect the coenzyme NAD(P)H with a detection limit of 1.0 μM.

This application discloses a photoactivator, its preparation method, and its application. The photoactivator has the structural formula shown in Formula I: X-Y-Z (Formula I); where X is a mitochondrial targeting group; Y is a linker arm; and Z is a photosensitizing group; the mitochondrial targeting group is connected to the photosensitizing group via the linker arm. The photoactivator provided in this application exhibits strong targeting of the mitochondrial proteome, good biocompatibility, and utilizes the high potential difference across the mitochondrial membrane to achieve enrichment within the mitochondria. Furthermore, it can generate singlet oxygen under visible light irradiation, avoiding non-specific reactions before the reagent reaches the target organelle.

The invention relates to a nano drug delivery system loaded with nitazoxanide as well as a preparation method and application of the nano drug delivery system, and belongs to the technical field of pharmaceutical preparations. The nano drug delivery system is prepared by loading nitazoxanide on a metal organic framework ZIF-90 nano material through a simple and rapid method. The nano drug delivery system constructed by the invention can effectively improve the solubility and stability of nitazoxanide, and realizes the enrichment of drugs in tumor cell mitochondria by virtue of the mitochondrial targeting characteristic of the ZIF-90 material. The system can intelligently release drugs under the acidic and high ATP conditions of a tumor microenvironment, not only utilizes the metabolic reprogramming effect induced by nitazoxanide, but also synergistically enhances the anti-tumor effect in cooperation with the Zn < 2 + >-triggered oxidative stress disorder dual mechanism, and provides a new strategy for solving the problems of low bioavailability, poor targeting property and the like in clinical application of nitazoxanide.

The invention belongs to the technical field of medicines, and particularly relates to lactylphenylalanine liposome with mitochondrial targeting and fluorescent tracing functions and application of the lactylphenylalanine liposome in treatment of metabolism-related fatty liver diseases. The preparation method comprises the following steps: firstly, preparing a bifunctional molecule Cy5-Lac Phe, and covalently linking a therapeutic active component with a mitochondrial targeting fluorescent tracing group through a chemical bond to form a single multifunctional entity; therefore, each therapeutic molecule is ensured to have targeting and tracing capabilities, and the problems of non-uniform targeting efficiency and in-vivo dissociation caused by simple physical mixing of different components are solved. According to the invention, the bifunctional molecules are prepared into liposome nanoparticles. According to the liposome, passive liver targeting is achieved through the nanometer size of the liposome, so that free Cy5-Lac Phe molecules are efficiently enriched and released in the liver, a Cy5 module plays a mitochondrial targeting function, and accurate drug delivery at the organelle level is achieved. Meanwhile, the fluorescent tracing function of Cy5 allows real-time visual monitoring of the medicine.

The invention discloses a bifunctional pesticide nanoparticle with mitochondrial targeting and pH response as well as a preparation method and application of the bifunctional pesticide nanoparticle. According to the invention, betaine is used as a novel mitochondrial targeting agent for the first time to construct a pesticide nano-carrier, and finally the pesticide nano-particles with mitochondrial targeting and pH response type dual functions are obtained. The prepared pesticide nanoparticles have the advantages of good biocompatibility, mild conditions, stable product morphology, realization of fixed-point targeted delivery, improvement of the pesticide utilization rate, and good application and popularization prospects.

The invention provides an AIE photosensitizer capable of inducing pyroptosis as well as a preparation method and application of the AIE photosensitizer. The preparation method comprises the following steps: carrying out a Knoevenagel condensation reaction between a corresponding aldehyde precursor and 4-pyridyl acetonitrile, and then treating with (4-bromobutyl) triphenyl phosphorus bromide to obtain the AIE photosensitizer capable of inducing pyroptosis. According to the AIE photosensitizer, a cationic side group is incorporated into a molecular structure, so that mitochondrial targeting can be realized; the AIE photosensitizer based on mitochondrial targeting shows powerful and efficient ROS (reactive oxygen species) generation; by generating high-concentration aggregated ROS in mitochondria, the mitochondrial targeting photosensitizer activates a caspase pathway to cause gasdermin lysis, then cells swell and release cell contents, and finally pyroptosis is induced, so that effective TSCC ablation can be realized.

The invention belongs to the technical field of cerebral apoplexy treatment medicine research, and particularly relates to a nano delivery system and application thereof. The nano delivery system is prepared according to the following steps: modifying cationic starch spheres with mitochondrial targeting peptide, loading PDK4-IN-1, and carrying out self-assembly to obtain an inner core; the preparation method comprises the following steps: modifying aminated anionic starch with homing peptide, and loading carfilzomib to form a starch spiral shell; and mixing the inner core with the starch spiral shell, and self-assembling to form the nano drug delivery system. According to the invention, a three-targeting, double-controlled-release and double-drug nano drug delivery system is constructed and is accurately delivered to a matrix action site in cytoplasm or mitochondria, so that double-channel synergistic enhancement of IS mitochondrial autophagy and toxicity attenuation and synergistic treatment of IS are realized.

The invention constructs a mitochondrial targeting metal immune drug (Mito-chaos), and the Mito-chaos is used for tumor treatment and wound repair. The core structure of the drug is Ca < 2 + > and Cu < 2 + > co-doped hollow Prussian blue nanoparticles (Ca / Cu-PB). The particle has a remarkable near-infrared (NIR) light response characteristic, can respond to 1064nm near-infrared light, and generates an efficient photothermal conversion effect. And furthermore, the Mito-chaos with the mitochondrial targeting capability is obtained by loading TPP modified Mito Cur in the pores of the Ca / Cu-PB nano particles, so that the Mito-chaos with the mitochondrial targeting capability is obtained. The Mito-chaos can be slowly degraded in a tumor acidic microenvironment (TME), releases Ca < 2 + > and Cu < 2 + > and delivers the Ca < 2 + > and the Cu < 2 + > into tumor cell mitochondria, induces homeostasis destruction of ions in the mitochondria, activates a tumor cell copper death pathway and plays an efficient tumor cell killing role. And meanwhile, the sustained-release Ca < 2 + > and Cu < 2 + > can play roles in promoting angiogenesis, promoting collagen deposition and improving tissue regeneration capacity, the postoperative wound healing speed is accelerated, and good tissue repair performance and clinical application potential of the medicine are embodied.

The application designs a series of xanthene near-infrared mitochondrial fluorescent tracers, the self-assembly characteristics of the dyes are regulated by the length of the external hydrophobic carbon chain, and then the stability of the mitochondrial targeting and the signal-to-noise ratio of the imaging are optimized. The fluorescent tracers show strong NIR fluorescence, the emission wavelength can reach 700 nm, the molar extinction coefficient is 10.9 M ‑1 *cm ‑1 *10 4 , the fluorescence quantum yield is 0.64. In the aqueous phase, the ACQ effect is significant, but it can be quickly enriched and embedded into mitochondria, and then the strong fluorescence is restored, showing high signal-to-noise ratio; in living cells, it has stable mitochondrial targeting, is not affected by the membrane potential, and the imaging performance is better than that of the commercial probe TMRM. The fluorescent tracer can accurately and stably trace the microtubular morphological changes of mitochondria in ferroptosis.

The invention provides a preparation method and application of a polymitochondrial targeting peptide PSS31 and a lung targeting nucleic acid drug delivery system, and belongs to the technical field of biochemical synthesis pharmacy. According to the invention, SS31 is polymerized through TK to form a polymer material sensitive to ROS (reactive oxygen species), namely the polymer mitochondrial targeting peptide PSS31. The PSS31 not only can efficiently load a nucleic acid drug through an electrostatic adsorption effect, but also can efficiently release the nucleic acid drug under the stimulation of ROS in cells. According to the invention, on the basis of the PSS31, a fucoidin (Fuco) modified lung-targeted nucleic acid drug delivery system siHIF-1alpha / PSS31 (at) Fuco is prepared through an electrostatic adsorption effect. The siHIF-1alpha / PSS31 (at) Fuco can be used for efficiently loading the siHIF-1alpha, improving the stability of the siHIF-1alpha, relieving pulmonary vascular remodeling, reducing pulmonary arterial pressure and efficiently treating hypoxic pulmonary hypertension in multiple ways.