17 results about "Calcium overload" patented technology

The present disclosure describes a new native peptide designated herein as Dwarf Open Reading Frame, or DWORF. This peptide enhances the apparent activity of the SERCA pump, is positively inotropic and lusitropic, and therefore is provided as a therapeutic agent for disorders characterized by cytosolic calcium overload.

The invention belongs to the field of biological medicine, and particularly relates to functionalized drug-loaded nanoparticles as well as a preparation method and application thereof. The macromolecule coupled folic acid modified quercetin-loaded mesoporous calcium carbonate nanoparticle T (at) QU (at) CaCO3 constructed by the invention not only can be used as a'calcium bomb 'to provide calcium ions for tumor calcium overload in a tumor slightly acidic environment, but also can be used for highly loading a traditional Chinese medicine anticancer active ingredient quercetin; besides, nanoparticles are wrapped based on polymer coupled folic acid modification, the stability of mesoporous calcium carbonate can be improved, irritation of quercetin can be reduced, in-vivo circulation can be enhanced, tumor cells can be further targeted based on folic acid modification, accumulation of drugs in TNBC cells can be promoted, and therefore the targeted delivery capacity is improved, and the purposes of effect enhancing and toxicity reducing are achieved. And a feasible scheme is provided for accurate targeted treatment of breast cancer, especially triple negative breast cancer.

The present application relates to a kind of plant source exosome-encapsulated drug-loaded calcium-based nanogenerator and preparation method and its application, the nanogenerator includes drug-loaded core, the drug-loaded core outside is coated with plant source exosome shell layer;Wherein, the plant source exosome shell layer is selected from one or more of curcuma source exosome, broccoli source exosome, artemisia annua source exosome, camellia source exosome.This nanogenerator of the present application has the ability of enhancing calcium overload and amplifying cell oxidative stress, the generator can improve the stability and biocompatibility of CaO2 While, overcome tumor cell antioxidant defense mechanism.By curcuma source exosome as protective layer wrapped outside CaO2, solve the problem of CaO2 In vivo blood circulation stability and dispersibility, increase the efficiency of the nanogenerator into tumor cell.

The present invention discloses a calcium carbonate-conjugated polymer composite nanoparticle with anti-tumor and anti-metastasis effects and its application. The nanoparticles rupture and decompose in the weakly acidic microenvironment of the tumor, releasing the conjugated polymer and a large amount of Ca 2+ The conjugated polymer can generate reactive oxygen species or heat energy to kill tumor cells under light. In addition, reactive oxygen species can also put tumor cells in a state of high oxidative stress, causing mitochondrial dysfunction and desensitization of calcium ion-related channels, causing intracellular "calcium overload" and inducing tumor cell death. These multiple effects make the nanoparticles highly effective in cancer treatment. Extracellular Ca 2+ Increased levels can enhance the adhesion between tumor cells by regulating the morphology of cadherin, thereby inhibiting tumor cell migration. In this invention, the calcium carbonate-conjugated polymer composite nanoparticles have excellent anti-tumor and anti-metastasis effects, providing a new approach for the comprehensive treatment of cancer.

The application relates to the field of nanobiomedical technology, and particularly relates to application of polyethylene glycol modified black phosphorus nanosheets in prevention and treatment of acute liver injury. The polyethylene glycol modified black phosphorus nanosheets not only have a significant active oxygen scavenging capacity, but also have calcium ion chelation and buffering capacity, can simultaneously regulate intracellular oxidation-reduction homeostasis and calcium homeostasis, inhibit intracellular calcium overload, especially mitochondrial calcium overload, maintain mitochondrial function, and further reduce liver cell damage, apoptosis and inflammatory response, and play a liver protection role. The application finds that the black phosphorus nanosheets are used in calcium ion chelation and inhibition of cell calcium overload, and breaks through the limitation that the black phosphorus nanosheets are mainly used as active oxygen scavenging materials in the prior art. The material can also adsorb copper ions and realize radioactivity copper labeling without chelating agent, and can be used for liver enrichment tracing and integrated diagnosis and treatment application. The material has a significant protective effect on paracetamol-induced acute liver injury.

This invention belongs to the field of biomedical nanomaterials and radiation damage drugs, specifically relating to a magnesium-ethylene glycol tetraacetic acid (EGTA) nanomedicine, its preparation method, and its applications. This study proposes using magnesium-EGTA nanomedicine to treat radiation dermatitis. EGTA's chelating ability for calcium ions is significantly higher than that of magnesium ions and other metal ions. Its unique ion selectivity provides an important theoretical basis and application potential for targeting and inhibiting mitochondrial calcium overload in the pathological process of radiation dermatitis. Magnesium ions are cofactors of many enzymes and have anti-inflammatory, collagen synthesis-promoting, and angiogenesis-enhancing effects. This study constructs a Mg-EGTA-based nanomedicine system, utilizing EGTA's stronger chelating ability for calcium ions, thereby achieving targeted regulation of mitochondrial calcium homeostasis through a calcium-magnesium ion intelligent replacement mechanism in response to calcium overload, providing new ideas and methods for the prevention and treatment of radiation dermatitis.

The application provides a metal polyphenol network-wrapped calcium peroxide nanoparticle and a preparation method and application thereof, and belongs to the technical field of tumor treatment. The metal polyphenol network-wrapped calcium peroxide nanoparticle has a protective effect on unstable calcium peroxide nanoparticles; the released metal ions catalyze hydrogen peroxide to generate hydroxyl radicals under acidic conditions, and then kill tumor cells, realize chemical kinetic therapy, can also consume glutathione, enhance the accumulation of active oxygen, and then enhance the anti-tumor effect; when dispersed into an acidic environment, the metal polyphenol network layer thereof can rapidly degrade, expose the calcium peroxide nanoparticles, and then explosively release a large amount of calcium ions and oxygen, which can more effectively activate calcium overload and relieve the tumor hypoxic microenvironment; by loading drugs, the effective accumulation of the drugs in the tumor site is improved, the combined treatment of chemical kinetic therapy and chemotherapy is realized, and thus the anti-tumor immune response is activated, and the anti-tumor effect is improved.

The present invention discloses a micellar mixed system for enhancing the therapeutic effect of irreversible electroporation on pancreatic cancer and a preparation method thereof. By mixing CGP37157-loaded PEG-PCL micelles (CGP37157@PEG-PCL) with a CaCl2 solution to form an injectable micellar mixed system, the poorly water-soluble CGP37157 sodium-calcium exchange inhibitor can be delivered into tumor cells. During electroporation therapy, as the permeability of tumor cells increases, the excretion of calcium ions in mitochondria is inhibited, further leading to mitochondrial calcium overload and accelerating tumor cell death. This can effectively improve the efficiency of IRE treatment and has good clinical application prospects.

The invention discloses application of naringenin in preparation of a medicine for preventing and treating cardiotoxicity induced by tacrolimus. The naringenin disclosed by the invention is a natural active matter, is non-toxic to cells, and has a potential heart protection effect of reversing, preventing and treating tacrolimus-induced cardiotoxicity; naringenin reduces expression of Cav1.2 on a membrane so as to influence a calcium signal channel and reverse calcium overload and cell apoptosis caused by tacrolimus; cav1.2 can be used as a target spot for preventing and treating cardiotoxicity induced by FK506, and the invention also prompts that overload calcium can be treated by using a corresponding calcium chelating agent, so that a theoretical basis is provided for the naringenin as a potential auxiliary medicine for tacrolimus application; the further deep research is expected to be beneficial to deep understanding of the action mechanism of the naringenin and provide more support for clinical application of the naringenin.

This invention discloses a targeted nanoparticle for calcium overload therapy combined with photothermal therapy, specifically involving a lipid-modified cRGD-targeting, MMP-responsive, and pH-sensitive calcium carbonate nanoparticle loaded with indocyanine green (ICG). This invention uses pH-sensitive calcium carbonate, which can decompose and exfoliate within lysosomes, as the matrix material. It leverages cRGD's specific targeting of tumor cells, the tumor microenvironment-specific high expression of matrix metalloproteinases (MMPs) to induce the release of DPPA-1 within the tumor microenvironment, and the low pH characteristic within lysosomes to achieve a combined anti-tumor effect of phototherapy and immunotherapy.

The invention discloses an MOF-based calcium ion nano regulator as well as a preparation method and application thereof. The preparation method comprises the following steps: step 1, preparing PCN-224; 2, preparing PCN-LA, wherein the PCN-LA is obtained by loading L-arginine (LA) on the surface of the nano material obtained in the step 1; 3, preparing PCN-LA-coated CaCO3, wherein the PCN-LA-coated CaCO3 is obtained by wrapping calcium carbonate (CaCO3) on the surface of the nano material obtained in the step 2; and 4, preparing the MOF-based calcium ion nano regulator: continuously modifying folic acid (FA) on the surface of the nano material obtained in the step 3 to obtain the MOF-based calcium ion nano regulator, which is called PLCF for short. According to the MOF-based calcium ion nano regulator, mitochondrial respiration can be inhibited by generating nitric oxide (NO), so that more intracellular oxygen is reserved for photodynamic therapy (PDT), calcium overload is continuously and efficiently induced, and calcium overload-photodynamic synergistic anti-tumor is realized. In a mouse in-vivo test, the nanoreactor can overcome the hypoxia environment of solid tumors and generate an excellent anti-tumor effect.

The invention relates to a phenolic acid-strontium nano-particle and a preparation method and application thereof, the phenolic acid-strontium nano-particle is a nano-structure obtained by self-assembly by using a method of modifying phenolic acid by metal strontium coordination, according to the prepared caffeic acid-strontium nanoparticles, coordination modification of phenolic acid molecules is achieved through coordination of strontium, carboxyl of phenolic acid and catechol groups, and the caffeic acid-strontium nanoparticles are of a spherical structure, small and uniform in particle size, good in dispersity, simple in preparation process, low in cost and easy to produce in batches; after the caffeic acid is subjected to coordination modification by strontium, the capability of targeted inhibition of the caffeic acid on the TRPV1 is remarkably enhanced, so that the problem of calcium overload of a focus is solved, and the problems of inflammatory polarization of macrophages and sensitization of damaged sensory neurons, which are caused by abnormal calcium influx due to high expression of the TRPV1 at the arthritis focus part, are effectively and synchronously solved; and the compound has excellent bone repair performance and extremely high biological safety, and has wide application prospects in preparation of drugs for preventing and / or treating inflammatory bone related diseases and preparation of bone repair drugs.

The present disclosure describes a new native peptide designated herein as Dwarf Open Reading Frame, or DWORF. This peptide enhances the apparent activity of the SERCA pump, is positively inotropic and lusitropic, and therefore is provided as a therapeutic agent for disorders characterized by cytosolic calcium overload.

The invention discloses a separated polypeptide for inducing mitochondrial calcium overload and application of the separated polypeptide. The separated polypeptide has an amino acid sequence as shown in SEQ ID NO: 1 or SEQ ID NO: 2. The separated polypeptide disclosed by the invention can be combined with NCLX protein, and degradation of the NCLX protein can be promoted through m-AAA protease, so that calcium ions can be prevented from being excreted, and calcium overload in mitochondria is avoided. In addition, the separated polypeptide is obviously superior to the existing calcium release inhibitor CGP37157 in the aspect of inducing mitochondrial calcium overload.

This invention discloses a calcium-chelating polydopamine-polyrotaxane nanoparticle, its preparation method, and its application, comprising the following steps: (1) aging dopamine hydrochloride in an alkaline solution, centrifuging to obtain polydopamine nanoparticles; dispersing cyclodextrin and bis-thiol-terminated polyethylene glycol in water, stirring at 0-5°C to prepare polyrotaxane; (2) reacting the obtained polydopamine nanoparticles with polyrotaxane in an alkaline solution to obtain polydopamine-polyrotaxane nanoparticles; (3) stirring the polydopamine-polyrotaxane nanoparticles with calcium salt in an alkaline solution to obtain calcium-chelating polydopamine-polyrotaxane nanoparticles. The nanoparticles prepared by the above method have long-term stable photothermal conversion capabilities and high calcium loading capacity, and can be used for tumor treatment through photothermal effect synergistic controllable calcium overloading.

The invention discloses bio-based nano composite hydrogel as well as a preparation method and application thereof, and relates to the technical field of biological materials. The nano composite hydrogel comprises a bio-based hydrogel carrier and a functional component loaded in the bio-based hydrogel carrier; the functional components comprise an oxidative stress enhancing functional component, a calcium overload inducing functional component and a targeting substance. The materials are synthesized, loaded and modified by methods such as a chemical reduction method, a stirring synthesis method, an in-situ generation method, an embedding method, a coprecipitation method, chemical crosslinking, a sol-gel method, Van der Waals' force, electrostatic interaction and the like. According to the nano-composite hydrogel, oxidative stress and calcium overload in tumors are jointly triggered and enhanced, tumor cells are directly killed, anti-tumor immune response is effectively activated, the process drives self-strengthening circulation of'treatment-immunization-retreatment ', and therefore the efficient and lasting anti-tumor effect is achieved.

The present invention belongs to the technical field of anti-cancer drugs, and specifically relates to a copper-manganese loaded calcium carbonate composite material, a preparation method thereof, and an application thereof. In the present invention, gallic acid, calcium carbonate nanoparticles, a water-soluble manganese salt, and a water-soluble copper salt are mixed to obtain copper-manganese loaded calcium carbonate nanoparticles; the copper-manganese loaded calcium carbonate nanoparticles are surface-modified with sodium dioleoyl phosphatide, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine, phospholipid polyethylene glycol, and (2,3-dioleoyloxypropyl) trimethyl ammonium chloride to obtain a copper-manganese loaded calcium carbonate composite material. In the present invention, the coated nanoparticles loaded with copper ions and manganese ions accumulate at the tumor site through the enhanced permeability and retention effect, realizing an efficient Fenton reaction. A large amount of ROS generated during the Fenton reaction will disrupt the intracellular Ca<supgt;2+< / supgt; balance, achieve calcium overload, and further cause mitochondrial dysfunction in tumor cells, realizing an efficient killing effect on tumor cells.