35 results about "Apoptotic body" patented technology

The invention belongs to the technical field of biological medicine, and discloses a high-efficiency vascular endothelial cell targeting vesicle system, which is prepared from hemangioma stem cell derived exosome HemSCs-Exos and bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs, and is characterized in that the endothelial cell targeting vesicle system is prepared from the hemangioma stem cell derived exosome HemSCs-Exos and the bone marrow mesenchymal stem cell derived apoptotic small body BMSCs-ABs; meanwhile, the invention further discloses a preparation method of the vesicle system and application of the vesicle system in promoting proliferation and migration of endothelial cells. Different from existing targeting modification, the ingenious targeting relationship between the BMSCs-ABs and the endothelial cells belongs to non-special modification combination, and is simple and efficient; the fusion between the double EVs has the characteristic of realizing '1 + 1gt, 2', not only retains the treatment components of the HemSCs-Exos and the BMSCs-ABs, but also the fused eHEs has remarkable cell specificity distribution, and the fusion mode is simple and stable.

The present invention provides compositions and methods for inducing antigen-specific tolerance in a subject. In one embodiment, the present invention provides a composition comprising an apoptotic body and an epitope of an antigen. Also provided herein are methods of preparing and administering the composition. The composition and methods provided herein can induce antigen-specific tolerance in a subject.

This invention relates to biomimetic mineralized exosomes for programmed drug penetration in tumors that inhibit cell burial, along with their preparation method and applications. Belonging to the field of novel excipients and dosage forms for pharmaceutical formulations, this invention co-loads the small-molecule chemotherapeutic drugs 10-hydroxycamptothecin and banoanthraquinone into exosomes. Then, through a biomimetic mineralization strategy, aTIM-4 is organically combined with mineralized calcium phosphate particles to obtain biomimetic mineralized exosomes. Under the acidic response of the tumor microenvironment, the calcium phosphate shell dissolves, and the exosome nucleus enters the tumor cells, inducing cell death and generating apoptotic bodies. This programmatically delivers the drug, delivering banoanthraquinone deep into the tumor. Simultaneously, the released aTIM-4 inhibits the cell burial of tumor-associated macrophages, amplifying the programmed drug penetration based on apoptotic bodies. This invention provides a new strategy and more options for overcoming the bottleneck of nanomedicine penetration in tumors, meeting the urgent clinical need for highly effective chemotherapeutic agents.

The invention relates to the technical field of biological medicines, and discloses application of a ZBP1 inhibitor in preparation of a medicine for treating cognitive impairment caused by plastics. Research finds that exposure of a specific dose of nano plastic can activate a ZBP1 signal channel in an organism and promote assembly of a pan-apoptosis small body compound, so that pan-apoptosis cascade reaction with pyroptosis, apoptosis and necrosis characteristics is triggered, and finally hippocampal neuron damage, dysfunction and learning and memory ability decline are caused. Further research shows that expression of key protein of pan-apoptosis can be remarkably inhibited through local injection of the ZBP1 inhibitor to the hippocampus, cognitive function impairment induced by nano-plastics is effectively improved, and the key effect of ZBP1 serving as a core factor in the regulation and control process is defined. Based on the discovery, the ZBP1 inhibitor can be used for preparing the medicine for treating the plastic pollution related cognitive impairment, and a brand new treatment strategy is provided for clinical intervention of the diseases.

The application discloses a kind of bioengineered apoptotic bodies based on apoptotic body membrane protein and liposome and preparation method and application thereof.The bioengineered apoptotic bodies are formed by the chimerization of apoptotic body membrane protein and liposome loaded with gastrodin and Cy5.The bioengineered apoptotic bodies simulating the natural apoptosis process of mesenchymal stem cells can promote the polarization of microglial cells to M2 type, release anti-inflammatory factors and neurotrophic factors, promote the proliferation of neurons, improve the antioxidant capacity of cells, improve the nervous motor function, relieve brain edema, and thus effectively treat traumatic brain injury.

Compositions of matter, devices, and treatment protocols for reducing deleterious effects of senescent cells in a mammal. The invention provides extracorporeal devices capable of removing, in some cases selectively, senescence associated factors including small molecules, proteins, lipoproteins, as well as in some embodiments extracellular vesicles including exosomes, apoptotic bodies, or cellular released particles. Extracorporeal removal of senescent cell associated factors is performed to augment effects of senolytic therapy. Removal of senescence associated factors is performed to enhance efficacy of regenerative medicine interventions.

Means of rejuvenating a subject through exposure to soluble factors or cell-free means, wherein the soluble factors are elaborated by immature or tolerogenic cells, and wherein the soluble factors comprise peptides, proteins, nucleic acids, microvesicles, nanovesicles, apoptotic bodies, and exosomes. Administration of the soluble factors is regenerative and to treat or prevent diseases associated with aging. Ultrasound can be utilized to enhance uptake, wherein said ultrasound may be delivered through extracorporeal shock wave therapy or other means. Cell secretions comprising soluble factors are collected from a bioreactor in which immature cells are viable in a basal state or stimulated by inflammatory or age-associated stimuli.

The invention discloses a phosphatidylserine modified gliadin nanoparticle as well as a preparation method and application thereof. The phosphatidylserine modified gliadin nanoparticle is of a core-shell structure, gliadin is entrapped by polylactic acid-glycolic acid copolymer to serve as a core, and a lipid composite membrane formed by phosphatidylserine and DSPE-PEG2000 is coated outside the nanoparticle. The gliadin-loaded nanoparticles modified by phosphatidylserine are used for simulating membrane signal characteristics of apoptotic bodies, enhancing recognition and uptake of the nanoparticles by macrophages and inducing tolerance phenotypic transformation of the nanoparticles, so that immune tolerance of celiac disease patients to gliadin is recovered, and the gliadin-loaded nanoparticles can be used for treating celiac disease patients. On the basis of simplifying the preparation process, the problems of unstable tolerance effect and lack of metabolic regulation in the existing nano immunotherapy are further solved. The nano-particles prepared by the technical route have good particle size distribution and stability, can effectively deliver antigens and induce immune tolerance, and are a novel convertible celiac disease treatment nano-preparation.

The application discloses a kind of for repairing cartilage decellularized cartilage matrix support and apoptotic corpuscle composition and its preparation method, composition includes: microporous support, support includes decellularized cartilage outer matrix and crosslinked organic polymer;Apoptotic corpuscle, apoptotic corpuscle exists in microporous support;Wherein, based on the volume 3.14mm 3 Microporous support, 0.01-0.02ug of apoptotic corpuscle is included.The combined support of the application can improve the activity of apoptotic corpuscle, prolong the action time of apoptotic corpuscle, achieve the effect of slow release, also can regulate joint cavity microenvironment, effectively promote joint cartilage repair, improve the repair effect of loss cartilage, avoid the security risks brought by traditional exogenous cell transplantation.

The invention relates to the technical field of biological medicine, in particular to an efficient macrophage targeting vesicle system as well as a preparation method and application thereof. The vesicle system is a chimeric vesicle (mHEs), and is prepared from extracellular vesicles (M2-EVs) derived from M2 type macrophages and apoptotic small bodies (MSC-ABs) derived from bone marrow mesenchymal stem cells. The vesicle system provided by the invention can realize specific recognition and functional regulation of macrophages, thereby playing an efficient therapeutic role in pathological processes such as tissue inflammation repair, myocardial infarction, ischemia-reperfusion injury and immune metabolism remodeling.

The invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and relates to a tumor programmed drug permeation biomimetic mineralization nano-vesicle capable of enhancing macropinocytosis as well as a preparation method and application of the tumor programmed drug permeation biomimetic mineralization nano-vesicle. The drug permeation biomimetic mineralization nano-vesicle is of a shell-core structure, chemotherapy drugs are co-loaded in the cell vesicle, and the exterior of the cell vesicle is encapsulated with a peptide fragment for specifically promoting the macropinocytosis of tumor cells through mineralization. The biomineralized cell membrane nano-vesicles which are good in stability and uniform in particle size are prepared, the calcium phosphate mineralized shell can specifically respond to tumor slightly acidic environment dissolution, and by enhancing the tumor macropinocytosis effect, uptake of apoptotic bodies by tumor cells is promoted, so that tumor apoptosis is promoted, and tumor apoptosis is inhibited. The apoptotic body-mediated drug has the advantages that the apoptotic body-mediated drug can be further improved in infiltration capacity in tumor tissues, programmed infiltration of the drug in the tumor tissues is realized, tumor growth is effectively inhibited, a great potential direction is provided for solving the tumor infiltration bottleneck of nano-drugs, and the apoptotic body-mediated drug has a good clinical application prospect.

The invention discloses an extraction method and application of membranous small vesicles. The extraction method comprises the following steps: collecting a biological sample, and selecting at least one of blood, urine and cell culture supernatant; centrifuging the sample at 10,000 xg for 20 minutes, and removing cell debris and apoptotic bodies to obtain a pretreated sample; adding 20% by volume of sample separation liquid and CD63 / CD81 antibody modified magnetic beads into the pretreated sample, and incubating and capturing target vesicles; freezing the captured vesicles with liquid nitrogen for 15-35 minutes, and dissolving the vesicles with a 33-43 DEG C water bath; and cracking the dissolved vesicles with 0.5 W / cm < 2 > ultrasonic waves to finally obtain the intact vesicles of 30-70 nm and soluble protein factors. Original plasma or urine can be directly treated, dilution is not needed, and loss of a target object is avoided; a low-cost and degradable biomimetic polymer is developed to replace an imported kit, and the cost is reduced by 75%; the whole process lt; the time is 2.5 hours, which is superior to that of an ultracentrifugation method; and the extracted membranous small vesicles have good integrity and are suitable for liquid biopsy and drug carrier construction.

The invention relates to the technical field of biological tissue engineering, in particular to a young mesenchymal stem cell-derived apoptotic body as well as a preparation method and application thereof. The apoptotic body is formed by inducing apoptosis of young mesenchymal stem cells through staurosporine. The apoptotic body can reduce the expression level of senescence-related factors and promote expression of matrix synthesis-related factors, so that a degeneration microenvironment is improved, extracellular matrix synthesis is promoted, and cell functions are improved. The apoptotic body can be applied to the field of delaying and reversing intervertebral disc degeneration, promotes repair and regeneration of intervertebral disc tissues by delivering rejuvenation signals, provides a new cell-free treatment strategy for treatment of intervertebral disc degeneration, avoids the risks of low cell survival rate, immunological rejection, tumorigenicity and the like, and has a good application prospect. Meanwhile, the traditional limitation of recovering tissue functions through physical or medicine means is broken through.

The invention belongs to the field of biological medicines, and particularly relates to application of apoptotic bodies derived from mesenchymal stem cells in preparation of medicines for preventing / treating keratitis. According to the invention, the bone marrow mesenchymal stem cells are induced by a chemical induction method, so that the bone marrow mesenchymal stem cells are subjected to apoptosis and apoptotic bodies are generated. Experiments prove that the apoptotic body derived from the bone marrow mesenchymal stem cells provided by the invention can realize inflammation regulation in bacterial keratitis by regulating polarization of macrophages, and a novel prevention and treatment method which is safer, easy to store and has a practical application effect is provided for treatment of the disease. The invention further provides a medicine for preventing / treating keratitis, the medicine takes the bone marrow mesenchymal stem cell-derived apoptotic body as an effective component, the medicine can be applied to high-risk patients who are prone to bacterial infection after corneal trauma in a pretreatment mode, and a prevention measure is provided for the high-risk exposure patients.

The application belongs to the technical field of biological medicine, and discloses a kind of high-efficiency vascular endothelial cell targeting vesicle system, which is prepared by hemangioma stem cell-derived exosome HemSCs-Exos and bone marrow mesenchymal stem cell-derived apoptotic body BMSCs-ABs, and the application further discloses a preparation method of the vesicle system and its application in promoting endothelial cell proliferation and migration. Unlike existing targeted modification, the ingenious targeting relationship between BMSCs-ABs and endothelial cells in the application belongs to the combination of non-special modification, which is simple and efficient. The fusion between double EVs has the characteristics of "1+1>2", which not only retains the therapeutic components of HemSCs-Exos and BMSCs-ABs, but also has a significant cell-specific distribution after fusion. The fusion method is simple and stable.

The invention discloses a bioengineering apoptotic body based on apoptotic body membrane protein and lipidosome as well as a preparation method and application of the bioengineering apoptotic body. The bioengineered apoptotic body is formed by chimeric combination of apoptotic body membrane protein and liposome loaded with gastrodin and Cy5. The bioengineered apoptotic body for simulating the natural apoptosis process of the mesenchymal stem cells is constructed, microglial cells can be promoted to be polarized to an M2 type, anti-inflammatory factors and neurotrophic factors are released, neuronal proliferation is promoted, the cell oxidation resistance is improved, the neuromotor function is improved, and encephaledema is relieved, so that traumatic brain injury is effectively treated.

This invention discloses a mitochondrial micro / nanoreactor system, its preparation method, and its applications. The system comprises mitochondrial-trained apoptotic bodies and a piezoelectric short-fiber scaffold, which are covalently linked via a copper-free click chemical linker. The mitochondrial-trained apoptotic bodies are obtained by inducing apoptosis in macrophages overexpressing Miro1 protein and pretreated with hypoxia, and are rich in functional mitochondria. The piezoelectric short-fiber scaffold is obtained by electrospinning a composite of poly-L-lactic acid and collagen, and can convert external mechanical energy into electrical signals. This invention, through synergistic action, on the one hand, utilizes apoptotic bodies to target and deliver functional mitochondria, enhancing intercellular mitochondrial transfer; on the other hand, it utilizes the piezoelectric effect to generate endogenous electrical stimulation, activating the mitochondrial autophagy pathway, thereby bidirectionally regulating mitochondrial energy metabolism homeostasis in diabetic wounds and significantly promoting wound healing.

In the body, adipose tissue is comprised of adipocytes as well as various other cell types, including immune cells, that may contribute to the overall extracellular vesicle pool. Adiponectin, a protein hormone produced by fat cells, and fatty acid binding protein 4 (FABP4) were selected as markers to isolate adipocyte- specific EVs / adipomes from the total pool of white adipose tissue-derived EVs based on in vitro data showing that they colocalized with Annexin V, an apoptosis marker, on the surface of budding apoptotic bodies. Intact L-adipomes (large- adipomes) and S-adipomes (small-adipomes) were successfully and selectively enriched from large-EVs and small-EVs, respectively. Immunoblotting analysis confirmed the presence of adiponectin, FABP4, Annexin V, and perilipin in both L- and S-adipomes, providing further evidence of their adipocyte origin.

Embodiments of the disclosure include treatments of subconcussive and / or concussive brain damage by administering fibroblasts and / or fibroblasts cultured with one or more types of immunocytes. In one specific embodiment fibroblasts are cultured with monocytes in the presence of patient-specific T cells, and subsequently the T cells are re-administered into the patient. In one particular embodiment, products derived from fibroblast-immunocyte mixtures are comprised of cellular lysate, apoptotic bodies, exosomes, and / or other microvesicles. In one embodiment, the fibroblast cells and / or products derived from the fibroblast cells are administered subsequent to one or multiple head injuries. In other embodiments, products are administered in combination with neurorestorative and / or neuroprotective interventions.

A microfluidic system can be used to quantify apoptotic bodies (ABs) with single-cell sensitivity, providing real-time information regarding the presence, and properties of ABs. Different subpopulations of ABs can thus be distinguished from one another to quantify cellular dis-assembly and drug sensitivity of the cancer cells under test. Impedance measurement can be performed by flowing secreted bodies at a substantially single-particle sensitivity. A plurality of electrical impedance magnitude and phase parameters of the biological sample can be measured within the flow cell structure, corresponding to a specified range of frequencies to help determine a biological characteristic of the cancer cells.

The invention belongs to the field of biological medicine, and particularly relates to a long-acting GnRH antagonist and a composition containing the same. According to the invention, a component with GnRH antagonistic activity is wrapped in a small apoptotic body derived from pituitary tumor cells, and it is found that the obtained preparation unexpectedly endows the active component with a longer in-vivo plasma half-life period; formulations prepared using small apoptotic bodies derived from other cell types such as mesenchymal stem cells, melanoma cells do not have this effect. On the basis, the GnRH antagonist disclosed by the invention can be further encapsulated in sustained-release microspheres, so that the in-vivo release behavior and bioavailability of the GnRH antagonist can be further optimized.

The application relates to the fields of biological medicine and tissue engineering materials, and particularly discloses a Janus microneedle capable of promoting inflammation subsiding and blood vessel regeneration of a diabetic wound surface as well as a preparation method and application of the Janus microneedle, the microneedle is a double-layer structure, the upper layer is loaded with an SLC7A11 inhibitor and an apoptotic body, and the lower layer is loaded with an engineered exosome overexpressing miR-17-5p. Through a unique double-layer hydrogel matrix design and a two-phase crosslinking process, the Janus microneedle realizes rapid release of active ingredients in the upper layer in the early healing stage to promote inflammation subsiding and phagocytosis, and slow release of active ingredients in the lower layer in the middle and late healing stage to continuously promote angiogenesis. The microneedle patch can intelligently simulate and synergistically regulate the natural timing of wound healing, solves the problem of space-time disconnection of the existing single therapy, and provides a novel and precise delivery strategy for efficient repair of chronic and difficult-to-heal wounds such as diabetes.

The invention provides an exosome extraction method and prepared exosome freeze-dried powder, and belongs to the technical field of exosome extraction. The invention provides an exosome extraction method which comprises the following steps: firstly, performing high-temperature stimulation on cells to improve secretion and release of exosomes; then the blood platelets subjected to high-temperature stimulation are subjected to circulating freeze thawing, so that most of cells, vesicles and the like are broken, and the integrity of the target product exosome is reserved; and filtering to remove impurities such as cell debris, apoptotic bodies and the like, and retaining an exosome product of 50-150nm. The invention also provides exosome freeze-dried powder which is prepared by freeze-drying the exosome product, and the purity of the exosome freeze-dried powder can reach 70-80%. By utilizing the exosome extraction method disclosed by the invention, the capacity of the exosome can be remarkably improved, and the method disclosed by the invention can be used for removing most impurities and retaining the integrity and activity of the exosome, so that the purity of the prepared exosome product is improved.

The application belongs to the field of biological medicine, and particularly relates to a double-effect compound capable of radiosensitization and protection against radiation injury, a composition containing the same and application thereof. The application first discovers that a compound with a molecular structure as shown in formula (I) has a double effect of radiosensitization and protection against radiation injury. Experiments prove that the material can significantly reduce the damage of ionizing radiation to normal nerve tissue, and can protect skin tissue and inhibit the occurrence and development of radiation dermatitis. Meanwhile, the compound has a unique advantage of penetrating the blood-brain barrier (BBB), and realizes the attenuation and synergistic effect of radiotherapy on brain tumors in in-vitro and in-vivo experiments. Further, the application innovatively combines the material with a small apoptotic body to construct a biomimetic delivery composition, which significantly improves the intracerebral delivery efficiency and target accumulation capacity of the double-effect compound through synergistic effect, and overcomes the technical bottleneck of brain-targeted delivery.(I)

The invention discloses a drug loading system based on natural apoptotic bodies (AB) and application of the drug loading system in glioma photodynamic therapy. The drug loading system contains apoptotic bodies modified by targeted peptide MFGM, and the amino acid sequence of the targeted peptide MFGM is shown as SEQ ID NO. 2. Preferably, the drug loading system also contains 5-aminolevulinic acid (5-ALA). According to the invention, a drug with a relatively high concentration is directly wrapped in the MFGM modified AB, on one hand, ANG2 and RGD in the MFGM can enhance BBB penetration and tumor targeting, on the other hand, consumption of the drug and generation of by-products are also avoided, and on the other hand, the MFGM modified AB transfers the target drug into target cells through a membrane fusion effect, so that the limitation of transmembrane transport of some drugs is overcome, and the drug delivery efficiency is improved. And the concentration of the drug in target cells is enhanced. Meanwhile, for some drugs with relatively strong side effects, AB limits the drugs in vesicles for transportation, and has no toxicity to normal cells and low side effects.

In the body, adipose tissue is comprised of adipocytes as well as various other cell types, including immune cells, that may contribute to the overall extracellular vesicle pool. Adiponectin, a protein hormone produced by fat cells, and fatty acid binding protein 4 (FABP4) were selected as markers to isolate adipocyte-specific EVs / adipomes from the total pool of white adipose tissue-derived EVs based on in vitro data showing that they colocalized with Annexin V, an apoptosis marker, on the surface of budding apoptotic bodies. Intact L-adipomes (large-adipomes) and S-adipomes (small-adipomes) were successfully and selectively enriched from large-EVs and small-EVs, respectively. Immunoblotting analysis confirmed the presence of adiponectin, FABP4, Annexin V, and perilipin in both L- and S-adipomes, providing further evidence of their adipocyte origin.

The invention relates to a double-layer detachable microneedle which comprises a soluble microneedle tip and a detachable hydrogel substrate layer, and the microneedle tip layer comprises at least one of drugs, extracellular vesicles, macromolecular substances and combinations of the drugs, the extracellular vesicles and the macromolecular substances. The extracellular vesicles are one or a combination of a plurality of exosomes, microvesicles, apoptotic bodies, autophagy-related extracellular vesicles, matrix vesicles and stress-related extracellular vesicles, and the macromolecular substances are one or a combination of a plurality of polypeptides, proteins, antigens, enzymes and antibodies. According to the double-layer detachable microneedle, early-stage antibiosis and pH adjustment can be achieved, infection is reduced, and inflammation is inhibited; macrophages are induced to be polarized from M1 to M2, and inflammation is promoted to be transited to a proliferation stage; needle tip loading is continuously released, and angiogenesis, cell proliferation and tissue regeneration are enhanced; the double-layer structure can sequentially respond to different stage requirements of the wound, and the healing efficiency of the diabetic wound is remarkably improved.

The invention belongs to the field of biological medicine, and particularly relates to a double-effect compound capable of radiosensitizing and preventing radioactive injury, a composition containing the double-effect compound and application of the double-effect compound. The invention firstly discovers that the compound with the molecular structure as shown in the formula (I) has dual effects of radiosensitization and radioactive damage prevention. Experiments prove that the material can significantly reduce damage of ionizing radiation to normal nervous tissues, can protect skin tissues, and can inhibit occurrence and development of radiodermatitis. Meanwhile, the compound has the unique advantage of penetrating through the blood-brain barrier (BBB), and the attenuating and synergistic effects on brain tumor radiotherapy are achieved in both in-vitro and in-vivo experiments. Furthermore, the material is innovatively assembled and combined with small apoptotic bodies to construct the bionic delivery composition, the intracerebral delivery efficiency and targeted accumulation capacity of the double-effect compound are remarkably improved through a synergistic effect, and the technical bottleneck of brain targeted delivery is overcome. # imgabs0 # (I)

The invention belongs to the field of medicine, and relates to the field of respiratory system disease treatment, in particular to a bionic drug delivery system based on drug combination of arsenic and NAC and application of the bionic drug delivery system in idiopathic pulmonary fibrosis. According to the bionic drug delivery system based on the combination of arsenic and NAC, apoptotic bodies derived from macrophages are used as carriers, and arsenic and NAC are sequentially loaded to obtain the bionic drug delivery system. In addition, the invention provides a preparation method of the bionic drug delivery system. The invention further provides application of the bionic drug delivery system to preparation of products for treating idiopathic pulmonary fibrosis. According to the invention, arsenic trioxide and NAC are innovatively combined for treating IPF, and the macrophage apoptosis body is used for preparing a bionic drug delivery system for reducing toxicity and enhancing efficacy. Results show that the bionic drug delivery system can enhance the targeting ability of the drug, so that the medication safety of the arsenic is improved, and meanwhile, the effect of the arsenic in IPF treatment is further improved.

The present application relates to a kind of engineered stem cell nanometer apoptotic bodies, its preparation method includes the following steps: by 3,3'-diindolylmethane directional induction obtains the engineered stem cell rich in repair and anti-inflammatory signal molecules, and then the engineered stem cell is induced to apoptosis, and the supernatant is separated and obtained by collection, then the programmed tandem extrusion process is handled to the engineered apoptotic body, and the particle size uniformity of the engineered nanometer apoptotic body is prepared.The engineered nanometer apoptotic body of the present application can effectively improve the microenvironment around hair follicle and regulate hair growth cycle, significantly improve the hair density and regeneration rate of androgenetic alopecia model mice, provide a new strategy of safe, convenient and efficient for clinical hair regeneration treatment.