CN113388571A - Liver targeted drug-loaded exosome and application and drug for treating liver diseases - Google Patents
Liver targeted drug-loaded exosome and application and drug for treating liver diseases Download PDFInfo
- Publication number
- CN113388571A CN113388571A CN202110693454.1A CN202110693454A CN113388571A CN 113388571 A CN113388571 A CN 113388571A CN 202110693454 A CN202110693454 A CN 202110693454A CN 113388571 A CN113388571 A CN 113388571A
- Authority
- CN
- China
- Prior art keywords
- liver
- exosome
- drug
- cells
- bile duct
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0693—Tumour cells; Cancer cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention belongs to the technical field of biological medicines, and provides a liver targeted drug-loading exosome and an application and a drug for treating liver diseases, wherein the liver targeted drug-loading exosome is obtained by introducing a drug for treating liver diseases into an exosome with liver tissue targeting property, and the exosome with the liver tissue targeting property is derived from gallbladder cells or bile duct cells; the medicine for treating liver diseases comprises the liver targeting medicine-carrying exosome; the exosome secreted by the gall bladder or the bile duct cells can be enriched in the liver without any modification, and the exosome derived from the gall duct cells is used, so that the problem of exosome yield is solved, and the exosome has a good application prospect; and the exosome from the bile cell can be used for loading different medicines or active molecules, and the medicine is delivered by targeting liver tissues, so that the treatment effect of liver diseases is improved, and the toxic and side effects of the medicines are reduced.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to a liver targeted drug-loading exosome, and an application and a drug for treating liver diseases.
Background
Liver disease is the collective term for all diseases that occur in the liver. Including infectious diseases, neoplastic diseases, vascular diseases, metabolic diseases, toxic diseases, autoimmune diseases, hereditary diseases, hepatolithiasis, etc. The infectious diseases include viral infection, bacterial infection, parasitic infection, etc., such as viral hepatitis, liver echinococcosis, etc. Liver cancer is the third most common malignant tumor with mortality rate second to that of stomach cancer and esophagus cancer, and the initial symptoms are not obvious, and the late symptoms mainly include symptoms of liver pain, hypodynamia, emaciation, jaundice, ascites and the like. The operation, the radiotherapy and the chemotherapy of western medicine and the traditional Chinese medicine combination therapy are generally adopted clinically, but the cure rate of patients in late stage is low due to the spread of cancer cells.
The traditional chemotherapy has the defects that the medicine is not specifically distributed, the target part is difficult to reach or is less reached, the blood concentration of the medicine in the body is low, the ideal treatment effect is often not achieved, and certain adverse reaction can be generated. The liver active targeting preparation as a novel drug delivery system can deliver drugs to liver cells in a targeted manner, improve the drug concentration of a target area and realize the effects of synergism and attenuation. In recent years, medical workers have been working on the development of liver targeted drug delivery systems. Existing liver targeting systems can be classified into hepatic parenchymal cell targeting drug delivery systems, hepatic non-parenchymal cell targeting drug delivery systems, and hepatic tumor cell targeting drug delivery systems.
For example, the liver parenchymal cell surface contains various receptors such as asialoglycoprotein receptor, glycyrrhetinic acid receptor and the like, and the liver active targeting of the medicine can be realized by utilizing the specific binding between the receptors and corresponding ligands thereof. The mannitol receptor belongs to a C-type lectin-like receptor, is named by the binding property of the mannitol receptor, exists on the surface of liver endothelial cells in a large amount, has wide binding specificity, and is used for targeted therapy by utilizing the mechanism. The monoclonal antibody is short for monoclonal antibody, is secreted by a hybridoma cell strain for identifying a specific antigenic determinant, has the characteristics of strong specificity, high sensitivity and the like, and is widely used in the field of biological medicine. The monoclonal antibody can be combined with radioactive isotopes, chemotherapeutic drugs, toxins and the like to form an immunoconjugate, which is one of the current therapeutic approaches for liver diseases. The monoclonal antibody in the antibody-mediated liver targeting drug delivery system is a main component, and the strength of the antibody directly influences the targeting treatment effect. The above targeting systems are all targeting realized at a molecular level, the targeting effect is not more than 30%, the targeting efficacy is low, and the off-target phenomenon exists. Therefore, the preparation of the drug-loading system which can effectively target liver tissues is an ideal choice for treating liver diseases, particularly liver cancer.
There are many current chemotherapeutic drugs for treating liver cancer, such as fluorouracil, doxorubicin, cisplatin, capecitabine, gemcitabine, irinotecan, oxaliplatin, and the like. Although the chemotherapeutic drugs have good antitumor effect, the weak targeting effect causes strong toxic and side effects in clinic.
Therefore, the preparation of a high-efficiency liver-targeting exosome drug-loading system for treating liver-related diseases is urgently needed.
Disclosure of Invention
The embodiment of the invention aims to provide a liver targeted drug-loading exosome, application thereof and a drug for treating liver diseases, so as to solve the problems in the background technology.
In order to achieve the above object, an embodiment of the present invention provides a liver targeting drug-loaded exosome, which is obtained by introducing a drug for treating a liver disease into an exosome with liver tissue targeting property, wherein the exosome with liver tissue targeting property is derived from gallbladder cells or bile duct cells.
Of course, the gallbladder cells or bile duct cells may also be genetically modified or engineered to target liver tissue, including but not limited to genetic modification, gene overexpression or deletion, molecular modification, etc.; exosomes of gall bladder or bile duct cells may also be surface modified or engineered to target liver tissue, including but not limited to surface protein modifications, surface protein alterations, surface small molecule modifications, and the like.
Preferably, the gallbladder cells or bile duct cells include, but are not limited to, human gallbladder cells, human bile duct cells, human gallbladder epithelial cell immortalized cells, hibebic, human gallbladder cancer cells, human bile duct cancer cells, animal gallbladder cells, animal bile duct cells, animal gallbladder cancer cells, animal bile duct cancer cells, induced pluripotent stem cell-induced gallbladder cells, and bile duct cells.
Preferably, the animals in the animal gallbladder cells, animal bile duct cells, animal gallbladder cancer cells, and animal bile duct cancer cells include, but are not limited to, monkeys, mice, hamsters, rats; the human gallbladder cancer cells include but are not limited to GBC-SD, NOZ, EH-GB1, SGC-996, OCUG-1; the human bile duct cancer cells include but are not limited to CCLP1, SK-ch-1, RBE, SK-chA-1, FRH-0201, QBC 939.
Preferably, the drug for treating liver diseases includes, but is not limited to siRNA, microRNA, protein, antibody, fluorouracil, doxorubicin, cisplatin, capecitabine, gemcitabine, irinotecan, oxaliplatin.
Preferably, the specific steps of introducing the drug for treating liver diseases into the exosome with liver tissue targeting are as follows:
putting a medicament for treating liver diseases and exosome with liver tissue targeting property into an electric rotor;
adopting exponential waves or square waves, and performing electrotransformation on the medicine for treating liver diseases and the exosomes with liver tissue targeting by using 50-300V voltage;
and (4) heating the electrotransformation product in water bath, centrifuging, and removing free drugs to obtain the purified liver targeting drug-loaded exosome.
The second purpose of the invention is to provide the application of the liver targeting drug-loaded exosome in the preparation of the drug for treating liver diseases.
The invention also provides a medicament for treating liver diseases, which comprises any one of the liver targeting medicament-loaded exosomes.
In summary, due to the adoption of the technical scheme, the method has the following beneficial effects:
the embodiment of the invention provides a liver targeted drug-loaded exosome and a drug for treating liver diseases, the liver targeted drug-loaded exosome can be enriched in the liver without any modification, and the exosome derived from gallbladder cells and bile duct cells is used, so that the problem of the yield of the exosome is solved, and the liver targeted drug-loaded exosome has good application prospect; and the exosomes from the gallbladder cells and the bile duct cells can be loaded with different medicines or active molecules, and the targeted liver tissue administration can improve the treatment effect of liver diseases and reduce the toxic and side effects of the medicines.
Drawings
FIG. 1 is a diagram showing the detection of exosome marker protein secreted by human gallbladder cancer cells GBC-SD.
FIG. 2 is a graph showing the measurement of the size distribution of exosomes secreted by human gallbladder cancer cells GBC-SD.
FIG. 3 is a map of PKH 67-labeled GBC-SD secreted exosomes in different tissues.
FIG. 4 is an in vitro assay of the antitumor activity of liver-targeted exosomes loaded with fluorouracil, a drug used to treat liver disease.
Figure 5 is an in vivo assay of the antitumor activity of liver-targeted exosomes loaded with fluorouracil, a drug used to treat liver disease.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the embodiments of the present invention are described in further detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the embodiments of the invention and are not limiting of the embodiments of the invention.
Example 1
The liver targeting drug-loading exosome is obtained by introducing a drug for treating liver diseases into an exosome with liver tissue targeting property, wherein the exosome with the liver tissue targeting property is derived from gallbladder cells or bile duct cells.
Exosomes secreted by human gallbladder cancer cells GBC-SD are collected, (in this example, human gallbladder cancer cells GBC-SD are selected as the cells secreting exosomes).
The GBC-SD cell culture solution is cultured by exosome-free serum and a DMEM medium; centrifuging at 2000g centrifugal force for 10min, and collecting supernatant; centrifuging for 30min under the centrifugal force of 10000g, taking supernatant, and removing cell debris and precipitates; centrifuging the centrifuged cell culture solution for 2h under 100000g of centrifugal force, re-suspending and collecting the precipitate by using sterile PBS, and storing at 4 ℃ for a short time to obtain the liver targeting exosome.
The liver targeting exosome surface marker protein isolated in example 1 was extracted and the particle size distribution thereof is shown in fig. 1 and 2. The amount of secreted exosome expressed by GBC-SD cells was measured, and the BCA method was used to detect the concentration of secreted exosome proteins (2.96. mu.g/. mu.L) secreted by GBC-SD cells.
Example 2:
the exosomes secreted by the GBC-SD cells in example 1-2 were taken, stained with PKH67, and the in vivo distribution of the exosomes secreted by the GBC-SD cells was traced, and C57bl/6 mice (4-6 weeks) were purchased from Beijing Wakumaokang Biotech GmbH, all of which were bred in SPF-grade facilities. The method comprises the following specific steps:
100 mu g of the exosome secreted by the GBC-SD cell is taken, incubated with 1 mu of LPKH674 ℃ overnight in the dark, centrifuged for 2h under 100000g (g is the gravity acceleration) of centrifugal force, the supernatant is discarded, washed twice by PBS, sterile PBS is used for re-suspending the exosome secreted by the bile cell, and the exosome is injected into a C57bl/6 mouse through the tail vein. After 24h, anesthetizing the mice, taking the heart, liver, spleen, lung, kidney, stomach and intestine of the mice to make frozen sections, staining nuclei by Hoechst33342, and observing the biological distribution of the exosomes secreted by the GBC-SD cells in each organ of the mice. The results show that: the exosome secreted by the GBC-SD cell is obviously enriched in liver tissues (figure 3), the targeting efficiency can reach 65% -90%, and the liver targeting exosome prepared by the embodiment of the invention has liver tissue targeting.
Example 3
The drugs for treating liver diseases include, but are not limited to, siRNA, microRNA, protein, antibody, fluorouracil, doxorubicin, cisplatin, capecitabine, gemcitabine, irinotecan, and oxaliplatin, and in this embodiment, the selected drug for treating liver cancer diseases is fluorouracil.
In the embodiment, the drug for treating liver diseases is introduced into a liver target exosome to prepare the liver tumor targeted therapeutic drug, and the specific operation is as follows:
1) 150 mu g of liver targeting exosome is mixed with fluorouracil, the electrotransfer buffer solution can be (PBS, DMEM, Cytomix, Tris-HCl) to complement the mixture to 150 mu L, and the mixture is transferred to electrotransfers with different specifications (0.2 cm and 0.4 cm). Adopting different waveforms (exponential waves and square waves) and using different voltages (50V, 100V, 200V and 300V) to respectively carry out electrotransformation on the liver targeting exosomes and the fluorouracil;
2) and (4) ultracentrifuging the electrotransformation product for 120 min under the centrifugal force of 100000g, and collecting the supernatant to measure the drug loading.
As a result: for fluorouracil, 150 mug of liver targeting exosome and fluorouracil are subjected to electrotransformation under the voltage of 250V, and the efficiency is the highest and can reach 33.8%. The results show that: fluorouracil was successfully loaded into exosomes secreted by GBC-SD cells.
Example 4
In this example, the therapeutic effect of the liver targeting exosome loaded with fluorouracil, a drug for treating liver diseases, on liver cancer was further verified through in vitro and in vivo experiments, in this example, Balb/c nude mice (4-6 weeks) were purchased from beijing waukang biotechnology limited, and all mice were cultured in SPF-level facilities. The method comprises the following specific steps:
in vitro experiments:
liver cancer cells HepG2 were plated in 96-well plates at 5X 10/well3And (3) adding a liver targeting exosome (a control group) and a liver targeting exosome loaded with the liver tumor treatment drug fluorouracil into each cell, and detecting the killing effect of the liver targeting exosome loaded with the liver tumor treatment drug fluorouracil on liver cancer cells by MTT (methyl thiazolyl tetrazolium). In vitro experiments, the liver targeting exosome loaded with the liver tumor treatment drug can effectively kill tumor cells compared with a pure liver targeting exosome, and the results are shown in fig. 4.
In vivo experiments:
in vivo experiments, a liver cancer model is established, and 5 × 10 is used6A HepG2 cell was injected subcutaneously into Balb/cNuded mice until they grew to approximately 100mm3In the meantime, liver targeting exosome loaded with fluorouracil as liver tumor treatment drug was injected into tail vein once every 3 days for 4 times, and then tumor volume was measured every other day, =1/2 × a × b2. a represents a long diameter, and b represents a short diameter.
In vivo experiments, as shown in fig. 5, the liver targeting exosome (fluorouracil-exosome) loaded with the liver tumor treatment drug fluorouracil can significantly reduce the tumor size of mice compared with the free antineoplastic drug group (fluorouracil) with equal dose.
It will be evident to those skilled in the art that the embodiments of the present invention are not limited to the details of the foregoing illustrative embodiments, and that the embodiments of the present invention are capable of being embodied in other specific forms without departing from the spirit or essential attributes thereof. The present embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the embodiments being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.
Furthermore, it should be understood that although the present description refers to embodiments, not every embodiment may contain only a single embodiment, and such description is for clarity only, and those skilled in the art should integrate the description, and the embodiments may be combined as appropriate to form other embodiments understood by those skilled in the art.
Claims (7)
1. The liver targeting drug-loaded exosome is characterized in that the liver targeting drug-loaded exosome is obtained by introducing a drug for treating liver diseases into an exosome with liver tissue targeting property, and the exosome with the liver tissue targeting property is derived from gallbladder cells or bile duct cells.
2. A liver targeting drug loaded exosome according to claim 1, wherein the gall bladder or bile duct cells include but are not limited to human gall bladder cells, human bile duct cells, human gall bladder epithelial cell immortalised cells, hibebic, human gall bladder cancer cells, human bile duct cancer cells, animal gall bladder cells, animal bile duct cells, animal gall bladder cancer cells, animal bile duct cancer cells, induced pluripotent stem cell induced gall bladder cells and bile duct cells.
3. The liver-targeted drug-loaded exosome according to claim 2, wherein the animal selected from the group consisting of animal gallbladder cells, animal bile duct cells, animal gallbladder cancer cells and animal bile duct cancer cells includes but is not limited to monkey, mouse, hamster, rat; the human gallbladder cancer cells include but are not limited to GBC-SD, NOZ, EH-GB1, SGC-996, OCUG-1; the human bile duct cancer cells include but are not limited to CCLP1, SK-ch-1, RBE, SK-chA-1, FRH-0201, QBC 939.
4. The liver targeted drug-loaded exosome according to claim 1, wherein the drug for treating liver disease includes but is not limited to siRNA, microRNA, protein, antibody, fluorouracil, doxorubicin, cisplatin, capecitabine, gemcitabine, irinotecan, oxaliplatin.
5. The liver targeted drug-loaded exosome according to claim 1, wherein the specific steps of introducing the drug for treating liver diseases into the exosome with liver tissue targeting property are as follows:
putting a medicament for treating liver diseases and exosome with liver tissue targeting property into an electric rotor;
adopting exponential waves or square waves, and performing electrotransformation on the medicine for treating liver diseases and the exosomes with liver tissue targeting by using 50-300V voltage;
and (4) heating the electrotransformation product in water bath, centrifuging, and removing free drugs to obtain the purified liver targeting drug-loaded exosome.
6. The use of a liver targeting drug loaded exosome according to any one of claims 1 to 5 in the preparation of a medicament for the treatment of a liver disease.
7. A medicament for treating liver diseases, comprising the liver-targeted drug-loaded exosome according to any one of claims 1 to 5.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110693454.1A CN113388571A (en) | 2021-06-22 | 2021-06-22 | Liver targeted drug-loaded exosome and application and drug for treating liver diseases |
| CN202210709497.9A CN115998893A (en) | 2021-06-22 | 2022-06-21 | Liver targeting drug-carrying exosome and application and drug for treating liver diseases |
| PCT/CN2022/100034 WO2022268056A1 (en) | 2021-06-22 | 2022-06-21 | Tissue-targeting exosomes and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110693454.1A CN113388571A (en) | 2021-06-22 | 2021-06-22 | Liver targeted drug-loaded exosome and application and drug for treating liver diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113388571A true CN113388571A (en) | 2021-09-14 |
Family
ID=77623379
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110693454.1A Withdrawn CN113388571A (en) | 2021-06-22 | 2021-06-22 | Liver targeted drug-loaded exosome and application and drug for treating liver diseases |
| CN202210709497.9A Pending CN115998893A (en) | 2021-06-22 | 2022-06-21 | Liver targeting drug-carrying exosome and application and drug for treating liver diseases |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210709497.9A Pending CN115998893A (en) | 2021-06-22 | 2022-06-21 | Liver targeting drug-carrying exosome and application and drug for treating liver diseases |
Country Status (1)
| Country | Link |
|---|---|
| CN (2) | CN113388571A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114949234A (en) * | 2021-12-01 | 2022-08-30 | 姜海涛 | Gallbladder-targeted drug-loaded exosome, application thereof and drug for treating gallbladder diseases |
| CN115475250A (en) * | 2022-05-26 | 2022-12-16 | 南京鼓楼医院 | Drug-loaded exosome for targeting hepatic stellate cells and inhibiting activation of hepatic stellate cells, and preparation and application thereof |
| WO2022268056A1 (en) * | 2021-06-22 | 2022-12-29 | 姜海涛 | Tissue-targeting exosomes and application thereof |
-
2021
- 2021-06-22 CN CN202110693454.1A patent/CN113388571A/en not_active Withdrawn
-
2022
- 2022-06-21 CN CN202210709497.9A patent/CN115998893A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022268056A1 (en) * | 2021-06-22 | 2022-12-29 | 姜海涛 | Tissue-targeting exosomes and application thereof |
| CN114949234A (en) * | 2021-12-01 | 2022-08-30 | 姜海涛 | Gallbladder-targeted drug-loaded exosome, application thereof and drug for treating gallbladder diseases |
| CN115475250A (en) * | 2022-05-26 | 2022-12-16 | 南京鼓楼医院 | Drug-loaded exosome for targeting hepatic stellate cells and inhibiting activation of hepatic stellate cells, and preparation and application thereof |
| CN115475250B (en) * | 2022-05-26 | 2024-03-26 | 南京鼓楼医院 | Drug-loaded exosome targeting hepatic stellate cells and inhibiting activation thereof, and preparation and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115998893A (en) | 2023-04-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113388571A (en) | Liver targeted drug-loaded exosome and application and drug for treating liver diseases | |
| US20210212948A1 (en) | Nanovesicles derived from cell membrane, and use thereof | |
| Wei et al. | Mononuclear phagocyte system blockade using extracellular vesicles modified with CD47 on membrane surface for myocardial infarction reperfusion injury treatment | |
| Liu et al. | The use of antibody modified liposomes loaded with AMO-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy | |
| JP2021503286A (en) | Method for producing MSC-derived exosomes | |
| Xin et al. | Mesenchymal stromal cell-derived extracellular vesicles modulate microglia/macrophage polarization and protect the brain against hypoxia-ischemic injury in neonatal mice by targeting delivery of miR-21a-5p | |
| US20180078508A1 (en) | Oncolytic virus formulation and preparation method thereof | |
| CN113846047A (en) | Kidney targeting drug-loaded exosome and application and drug for treating kidney diseases | |
| CN113521294A (en) | Stomach targeting drug-loaded exosome and application and drug for treating stomach diseases | |
| CN114129734A (en) | Gallbladder tissue targeted drug-loaded exosome and preparation method and application thereof | |
| CN110652492A (en) | Drug-loaded exosome, application thereof and liver disease drug | |
| CN113476615A (en) | Lung targeting drug-loaded exosome and application and lung disease treatment drug | |
| Huang et al. | Rat bone mesenchymal stem cell-derived exosomes loaded with miR-494 promoting neurofilament regeneration and behavioral function recovery after spinal cord injury | |
| CN108175759A (en) | A kind of antineoplastic target drug delivery system and preparation method and application | |
| CN114958722B (en) | Colorectal targeting drug-carrying exosome and application and drug for treating colorectal diseases | |
| CN113355290A (en) | Anti-tumor engineered exosome, preparation method and application | |
| CN113398092A (en) | Bladder targeted drug-loaded exosome and application and drug for treating bladder diseases | |
| CN110016465A (en) | A kind of immunocyte drug comprising B cell and the double identity T cells of tumour | |
| CN107913284B (en) | Application of miRNA302-367 cluster microRNA in targeted inhibition of angiogenesis and tumor growth | |
| WO2023051822A1 (en) | Targeting oligonucleotide for treating diseases associated with pcsk9 | |
| CN114081959A (en) | Pancreas targeted drug-loaded exosome, and preparation method, application and carrier thereof | |
| CN103405787B (en) | Molecular targeted nucleic acid nano-medicament based on miR-141 (micro ribonucleic acid-141), preparation and application thereof | |
| EP1568379A1 (en) | Medicinal preparation having chemotherapeutic encapsulated therein | |
| CN113633654A (en) | Targeted drug and preparation method and application thereof | |
| CN1896100B (en) | Liver regenerated factor and its use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WW01 | Invention patent application withdrawn after publication | ||
| WW01 | Invention patent application withdrawn after publication |
Application publication date: 20210914 |