CN116785257B - Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereof - Google Patents
Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereofInfo
- Publication number
- CN116785257B CN116785257B CN202310798869.4A CN202310798869A CN116785257B CN 116785257 B CN116785257 B CN 116785257B CN 202310798869 A CN202310798869 A CN 202310798869A CN 116785257 B CN116785257 B CN 116785257B
- Authority
- CN
- China
- Prior art keywords
- mesenchymal stem
- stem cell
- cisplatin
- umbilical cord
- cord mesenchymal
- 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.)
- Active
Links
Landscapes
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明提供了一种脐带间充质干细胞外泌体与顺铂的复合物及其制备方法和应用，所述脐带间充质干细胞外泌体包裹顺铂得到脐带间充质干细胞外泌体与顺铂的复合物，所述复合物的制备方法包括以下步骤：1）提取脐带间充质干细胞外泌体；2）按1：1的质量比，将所述脐带间充质干细胞外泌体和顺铂混合得到混合物；3）采用超声法对所述混合物进行超声处理，超声结束后离心处理弃去上清液，得到所述复合物，所述复合物还可以作为治疗宫颈癌的药物。本发明提供的一种脐带间充质干细胞外泌体与顺铂的复合物具有良好的生物相容性、高稳定性和良好的靶向性，能够将顺铂定向运输至病灶部位，降低顺铂的毒副反应，对妇科肿瘤有很好的抑制作用。
This invention provides a complex of umbilical cord mesenchymal stem cell exosomes and cisplatin, its preparation method, and its application. The umbilical cord mesenchymal stem cell exosomes encapsulate cisplatin to obtain the complex. The preparation method of the complex includes the following steps: 1) extracting umbilical cord mesenchymal stem cell exosomes; 2) mixing the umbilical cord mesenchymal stem cell exosomes and cisplatin at a 1:1 mass ratio to obtain a mixture; 3) sonicating the mixture using ultrasound, followed by centrifugation to discard the supernatant, obtaining the complex. The complex can also be used as a drug for treating cervical cancer. The umbilical cord mesenchymal stem cell exosome and cisplatin complex provided by this invention has good biocompatibility, high stability, and good targeting, enabling targeted delivery of cisplatin to the lesion site, reducing the toxic side effects of cisplatin, and exhibiting a good inhibitory effect on gynecological tumors.
Description
Technical Field
The invention belongs to the field of biomedicine, and particularly relates to a compound of umbilical cord mesenchymal stem cell exosomes and cisplatin, and a preparation method and application thereof.
Background
Cisplatin (cis-diamminedichloroplatinum (II), CDDP) was first approved by the U.S. food and drug administration in 1978 for the treatment of testicular and bladder cancers, and has found wide clinical use thereafter. As a broad-spectrum antitumor drug, cisplatin plays a role in inhibiting tumor growth mainly by combining with tumor cell DNA into a complex, causing DNA damage and further causing mitochondrial apoptosis, and generating cytotoxicity.
Cisplatin has weak targeting effect, so that the cisplatin has strong toxic and side effects clinically and can cause drug resistance of tumors. In general, in the early stage of cisplatin treatment of tumors, the tumor growth is significantly inhibited, even the solid tumors are significantly reduced, and the patient's condition is relatively stable in the initial stage of treatment. However, as treatment continues, a significant portion of the tumors that were initially cisplatin sensitive eventually develop drug resistance, a phenomenon that is particularly pronounced in ovarian cancer patients.
While exosomes are vesicles secreted by a variety of cells, with phospholipid bilayer structures and nanoparticle sizes. The nano-drug delivery system has good biocompatibility, high stability and good targeting property, plays an important role in drug targeting delivery, enhancing the bioavailability of the drug and the like, and can be used for transporting cisplatin to focus positions. However, the application of mesenchymal stem cell exosomes to platinum drug delivery has not been specified, and the application of mesenchymal stem cell exosomes to gynecological tumors such as cervical cancer has not been studied.
Disclosure of Invention
The invention aims to solve the technical problem of providing a compound of umbilical cord mesenchymal stem cell exosomes and cisplatin, and a preparation method and application thereof, and aims to use the umbilical cord mesenchymal stem cell exosomes to wrap cisplatin and transport the cisplatin to focus positions, so that the drug resistance of gynecological tumors to cisplatin is greatly reduced.
In order to solve the technical problems, the invention is realized in such a way that the umbilical cord mesenchymal stem cell exosome is in a compound with cisplatin, and the umbilical cord mesenchymal stem cell exosome is wrapped with cisplatin.
The invention also provides a method for preparing the complex of umbilical mesenchymal stem cell exosomes and cisplatin, which comprises the following steps:
1) Extracting umbilical cord mesenchymal stem cell exosomes;
2) Mixing the umbilical cord mesenchymal stem cell exosome and cisplatin according to a mass ratio of 1:1 to obtain a mixture;
3) And carrying out ultrasonic treatment on the mixture by adopting an ultrasonic method, and centrifuging after ultrasonic treatment is finished to remove supernatant fluid to obtain the compound.
Further, umbilical cord mesenchymal stem cell exosomes were extracted according to the following steps:
1.1 Culturing umbilical cord tissue to obtain umbilical cord mesenchymal stem cells;
1.2 Performing subculture on the umbilical cord mesenchymal stem cells by using a human umbilical cord mesenchymal stem cell complete medium;
1.3 Separating and extracting umbilical cord mesenchymal stem cell culture solution obtained by subculture by using an exosome extraction kit to obtain umbilical cord mesenchymal stem cell exosomes.
Further, ethyl acetate, lysine and fructose in the mass-volume ratio of 0.1-15%, 0.2-5% and 0.2-2% are added to the mixture obtained in step 2) before the ultrasonic treatment of step 3).
Further, the degassing treatment is performed simultaneously with the ultrasonic treatment in the step 3).
Further, the step 3) is carried out with ultrasonic treatment at 20 KHz.
Further, the ultrasonic treatment is carried out for a plurality of times, 6S/time, and the ultrasonic treatment is placed on ice for balancing for 3-15min after each ultrasonic treatment.
Further, after the end of the ultrasonic treatment in the step 3), the ultrasonic treatment was performed for 40min under a centrifugal force of 13500 g.
The invention also provides application of the umbilical mesenchymal stem cell exosome and cisplatin compound in preparing a medicament for treating cervical cancer.
Compared with the prior art, the compound of umbilical mesenchymal stem cell exosome and cisplatin and the preparation method and application thereof have the beneficial effects that:
The invention provides a compound of umbilical cord mesenchymal stem cell exosomes and cisplatin, a preparation method and application thereof, wherein the umbilical cord mesenchymal stem cell exosomes wrap cisplatin to obtain the compound of umbilical cord mesenchymal stem cell exosomes and cisplatin, and the preparation method of the compound comprises the following steps of 1) extracting umbilical cord mesenchymal stem cell exosomes, 2) mixing the umbilical cord mesenchymal stem cell exosomes and cisplatin according to the mass ratio of 1:1 to obtain a mixture, 3) carrying out ultrasonic treatment on the mixture by adopting an ultrasonic method, and centrifuging supernatant after ultrasonic treatment to obtain the compound, wherein the compound can also be used as a medicament for treating cervical cancer. The complex of umbilical mesenchymal stem cell exosome and cisplatin provided by the invention has good biocompatibility, high stability and good targeting property, can directionally transport cisplatin to focus positions, reduces toxic and side effects of cisplatin, and has good inhibition effect on gynecological tumors.
Drawings
FIG. 1 is a graph showing the particle size distribution of umbilical cord mesenchymal stem cell exosomes in example 1 of the present invention;
FIG. 2 is a surface topography of umbilical cord mesenchymal stem cell exosomes in example 1 of the present invention;
FIG. 3 is a graph showing the detection of a marker protein of umbilical cord mesenchymal stem cell exosomes in example 1 of the present invention;
FIG. 4A is a HPLC chart of cisplatin standard in example 2 of the present invention;
FIG. 4B is a graph of HPLC detection of cisplatin in the supernatant of the complex of umbilical cord mesenchymal stem cell exosomes and cisplatin in example 2 of the present invention;
FIG. 5A is a graph showing the efficiency of encapsulation of cisplatin by umbilical cord mesenchymal stem cell exosomes in example 3 of the present invention;
FIG. 5B is a graph showing the comparison of cisplatin content in the complexes of umbilical cord mesenchymal stem cell exosomes and cisplatin immediately after cisplatin-coated treatment and after seven days of stable storage in example 3 of the present invention;
FIG. 6 is a graph showing the effect of the complex of umbilical cord mesenchymal stem cell exosomes and cisplatin on the proliferation of cervical cancer cells Hela at 24h and 48h in example 4 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1 extraction and detection of umbilical mesenchymal Stem cell exosomes
Firstly, the specific steps of extracting umbilical mesenchymal stem cell exosomes are that fresh healthy human umbilical cord is taken, PBS is used for washing the umbilical cord cleanly, scissors forceps are used for removing blood vessels in the umbilical cord, and Fahrenheit rubber tissues in the umbilical cord are peeled off to obtain umbilical cord tissues. Umbilical cord tissue was thoroughly minced to 1mm x 1mm size, and placed in a 37 ℃ 5% CO 2 incubator with alpha-MEM broth containing 15% FBS,100U/ml penicillin and 100U/ml streptomycin. After 5-7 days of umbilical cord tissue culture, it can be seen that some cells climb out from the periphery of umbilical cord tissue in a form of fine shuttles, after 7 days, the cells begin to proliferate rapidly to form cell colonies of different sizes, after the cells grow up, the subcultured cells are digested with 0.25% trypsin, and the subsequent subculture is performed using human umbilical cord mesenchymal stem cell complete medium (serum-free type II) purchased from Sai-Biotech Co., ltd., cat No. HUXUC-90062. Collecting umbilical cord mesenchymal stem cell culture solution from human umbilical cord mesenchymal stem cell complete culture medium, placing on ice, centrifuging for 10min under 2000g centrifugal force, removing residual cells, collecting supernatant, centrifuging for 10min under 10000g centrifugal force, removing cell debris, and collecting supernatant again. The umbilical cord mesenchymal stem cell exosomes in the supernatant are separated and extracted by adopting a cell culture fluid exosome extraction kit, and the specific operation steps are as follows:
a. Transferring the supernatant to a new centrifuge tube, adding Isolation Regent A liquid with the volume ratio of 2:1 (V Sample : VA =2:1);
b. Mixing for 3-5 times, standing at 4deg.C for 5min, centrifuging at 10000g centrifugal force for 3 min min, transferring supernatant to a new centrifuge tube, and adding Isolation Regent B solution with volume ratio of 1:1;
c. mixing for 3-5 times, standing at 4deg.C for 1 hr, centrifuging at 13500 g under centrifugal force for 0.5: 0.5 h, discarding supernatant, and collecting precipitate which is umbilical mesenchymal stem cell exosome;
d. 200-500ul of sterile PBS was added to resuspend the pellet according to subsequent experiments, and subsequent experiments were performed or stored at-80℃after sub-packaging.
After successful extraction of umbilical cord mesenchymal stem cells, the umbilical cord mesenchymal stem cells are identified:
The umbilical cord mesenchymal stem cell exosome is identified by adopting a nanometer particle size tracker (NTA), a Transmission Electron Microscope (TEM) and a western blotting technology (WB), and the particle size distribution, the surface morphology and the marker proteins of the umbilical cord mesenchymal stem cell exosome are tested to obtain the umbilical cord mesenchymal stem cell exosome shown in figures 1,2 and 3.
Example 2 preparation of complexes of umbilical mesenchymal Stem cell exosomes and cisplatin
The experimental group comprises the steps of mixing umbilical mesenchymal stem cell exosomes and cisplatin (organisms) according to a mass ratio of 1:1, adding 0.1-15 g of ethyl acetate, 0.2-5 g of lysine and 0.2-2g of fructose into each 100ul of mixed solution, and performing intervention on the mixed solution by adopting an ultrasonic method, wherein the specific parameters are 20KHZ, degassing treatment, 6S/times and ultrasonic treatment for 4 times (repeated 3 times), and balancing on ice for 5min after each ultrasonic treatment. After the ultrasonic treatment is finished, 13500g is centrifugated for 40min after the room temperature is balanced for 30min, the supernatant and the sediment are separated, and the obtained sediment is a compound of umbilical mesenchymal stem cell exosomes and cisplatin of an experimental group.
And in the control group, umbilical mesenchymal stem cell exosomes and cisplatin (organisms) are mixed according to a mass ratio of 1:1, then an ultrasonic method is adopted to intervene on the mixed liquid, the specific parameters of the ultrasonic method are 20KHZ, degassing treatment, 6S/time, ultrasonic treatment is carried out for 4 times (repeated for 3 times), and the mixed liquid is placed on ice for balancing for 5min after each ultrasonic treatment. After the ultrasound is finished, 13500g is centrifugated for 40min after being balanced for 30min at room temperature, supernatant and sediment are separated, and the obtained sediment is a compound of umbilical mesenchymal stem cell exosomes and cisplatin of a control group.
The complex of umbilical cord mesenchymal stem cell exosomes and cisplatin of the experimental group is subjected to high-speed centrifugation for 30min under the centrifugal force of 13500g, the cisplatin content in the supernatant is collected, the content of cisplatin loaded by the mesenchymal stem cell exosomes is analyzed by adopting a High Performance Liquid Chromatography (HPLC), the efficiency of cisplatin loaded by the mesenchymal stem cells is further analyzed, and the HPLC detection parameters are as follows:
Chromatographic column C18 (4.6 mm×250mm,5 μm), column temperature 30 ℃, acetonitrile as mobile phase: water=30:70, flow rate 1.5ml/min, detection wavelength 270nm, sample injection amount 20 μl, detection results shown in fig. 4, fig. 4A is a cisplatin standard HPLC detection chart in this example, and fig. 4B is a cisplatin HPLC detection chart in a complex supernatant of umbilical mesenchymal stem cell exosomes and cisplatin in this example.
Example 3 detection of efficiency and stability of encapsulation of cisplatin by umbilical mesenchymal Stem cell exosomes
The complexes of umbilical cord mesenchymal stem cell exosomes and cisplatin in the control group and the experimental group in example 2 were centrifuged at a high speed for 30min under a centrifugal force of 13500g, and the cisplatin content in the supernatant was detected by High Performance Liquid Chromatography (HPLC), and the encapsulation efficiency of the umbilical cord mesenchymal stem cell exosomes on cisplatin, namely, the drug loading rate was = (1-cisplatin content in supernatant/total cisplatin content) = (100%). The result of the encapsulation efficiency of the umbilical cord mesenchymal stem cell exosome on cisplatin is shown in figure 5A, wherein the encapsulation efficiency of the control group is 46%, the encapsulation efficiency of the experimental group is 63%, and it can be seen that after the umbilical cord mesenchymal stem cell exosome and cisplatin are conventionally mixed, ethyl acetate with the mass-volume ratio of 0.1% -15% is added, and the encapsulation efficiency of lysine and fructose with the mass-volume ratio of 0.2% -5% on cisplatin of the umbilical cord mesenchymal stem cell exosome is improved.
After the complex precipitate of umbilical cord mesenchymal stem cell exosomes and cisplatin in the control group and the experimental group in example 2 are respectively stably stored at 4 ℃ for seven days, 200ul of pure water is added, high-speed centrifugation is performed for 30min under the centrifugal force of 13500g, cisplatin in the supernatant is collected, the content of cisplatin in the exosomes after seven days of storage is detected, and the stability of the umbilical cord mesenchymal stem cell exosomes coated cisplatin is calculated by comparing with the content of cisplatin in the control group and the experimental group detected in example 2. The stability test result of cisplatin coated by umbilical cord mesenchymal stem cell exosomes is shown in fig. 5B, wherein the cisplatin loading stability of the control group is about 78%, and the cisplatin loading stability of the experimental group is about 83%. According to experimental data, after the umbilical cord mesenchymal stem cell exosome and cisplatin are mixed conventionally, ethyl acetate with the mass-volume ratio of 0.1% -15% and lysine with the mass-volume ratio of 0.2% -5% and fructose with the mass-volume ratio of 0.2% -2% are added, so that the cisplatin load stability of the umbilical cord mesenchymal stem cell exosome can be effectively improved.
Example 4 experiments on inhibition of proliferation of cervical cancer cells Hela by umbilical mesenchymal Stem cell exosome-cisplatin Complex
HeLa cells were grown by trypsinization with 0.25% EDTA and incubated 5 min in a 37℃5% CO 2 incubator. When the round shrinkage of the Hela cells was observed under an inverted microscope, the digestion with trypsin was terminated by adding DMEM medium containing 10% FBS, after the Hela cells were blown down to complete shedding, the culture broth was collected and transferred to a 5ml sterile centrifuge tube, centrifuged at 1000rmp/min for 5 minutes, and the supernatant was discarded.
HeLa cells were resuspended in medium containing 3% FBS, and after fixing the volume, the cells were counted in a blood cell counting plate and plated in 96-well plates (1X 10 4 cells/well). After the culture plates were transferred into a constant temperature incubator and incubated for 12h at 37 ℃ under 5% CO 2 and saturated humidity conditions, the supernatant was discarded, a cisplatin solution with a final concentration of cisplatin of 10uM, a culture solution of a complex of umbilical cord mesenchymal stem cell exosomes and cisplatin (MSC-Exo-cisplatin complex culture solution) and an equivalent amount of umbilical cord mesenchymal stem cell exosomes culture solution of 100ug/ml (MSC-Exo culture solution) were added respectively, a multiplex well of 3 culture solutions with different concentrations was established for each group, after the culture plates were continuously transferred into the incubator and incubated for 24h, 5g/L MTT 20ul was added for 24h, after the culture was continued for 4h, the supernatant was sucked, 150ul DMSO solution was added, the culture plates 10 min were oscillated, absorbance values were detected with a microplate reader, absorbance values were measured for each well, absorbance values (OD) were measured, proliferation rates of Hela cells=absorbance values for each well of the experimental group/control group, absorbance values for each well were calculated, and the proliferation inhibition rates of hela=100 h were calculated for hela=100 h.
The absorbance per well of each group at 48h of incubation time was measured by the same method, and the inhibition rate of Hela cells at 48h was calculated. FIG. 6 is a graph showing the effect of the complex of umbilical cord mesenchymal stem cell exosomes and cisplatin on the proliferation of cervical cancer cells Hela cells at 24h and 48h in this example, and the ordinate of FIG. 6 shows the proliferation rate of Hela cells. The culture time was 24 hours, the proliferation rate of HeLa cells in MSC-Exo culture solution was about 105%, the proliferation rate in cisplatin solution was about 96%, and the proliferation rate in MSC-Exo-cisplatin complex culture solution was only 60%, and it was found that cisplatin solution was far less effective than MSC-Exo-cisplatin complex culture solution in inhibiting proliferation of HeLa cells. The culture time is 48h, the proliferation rate of the HeLa cells in the MSC-Exo culture solution is about 81%, the proliferation rate of the HeLa cells in the cisplatin solution is about 86%, and the increase of the time proves that the cisplatin can inhibit the HeLa cells, but the efficiency of inhibiting the HeLa cells gradually decreases, and the proliferation rate of the HeLa cells in the MSC-Exo-cisplatin complex culture solution is 47%, so that the inhibition effect of the MSC-Exo-cisplatin complex culture solution on the HeLa cells is far higher than that of the cisplatin solution. The experimental result proves that the umbilical cord mesenchymal stem cells coated with cisplatin have obvious inhibition effect on gynecological tumor cells, and the inhibition effect and the long-term inhibition capability are far better than those of cisplatin.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (6)
1. A method for preparing a complex of umbilical cord mesenchymal stem cell exosomes and cisplatin, comprising the steps of:
1) Extracting umbilical cord mesenchymal stem cell exosomes;
2) Mixing the umbilical mesenchymal stem cell exosome and cisplatin according to a mass ratio of 1:1, and adding ethyl acetate, lysine and fructose with mass and volume ratio of 0.1% -15%, and obtaining a mixture;
3) And carrying out ultrasonic treatment on the mixture by adopting an ultrasonic method, and centrifuging after ultrasonic treatment is finished to remove supernatant fluid to obtain the compound.
2. The method according to claim 1, wherein umbilical mesenchymal stem cell exosomes are extracted according to the following steps:
1.1 Culturing umbilical cord tissue to obtain umbilical cord mesenchymal stem cells;
1.2 Performing subculture on the umbilical cord mesenchymal stem cells by using a human umbilical cord mesenchymal stem cell complete medium;
1.3 Separating and extracting umbilical cord mesenchymal stem cell culture solution obtained by subculture by using an exosome extraction kit to obtain umbilical cord mesenchymal stem cell exosomes.
3. The method according to claim 1, wherein the degassing treatment is performed simultaneously with the ultrasonic treatment in the step 3).
4. The method of claim 1, wherein the step 3) is performed at 20 KHz.
5. The method of claim 4, wherein the sonicating is performed a plurality of times, 6S/time, and the sonicating is performed on ice for 3-15 minutes after each sonication.
6. The method according to claim 1, wherein the centrifugation is performed at 13500g centrifugal force for 40min after the end of the ultrasound in step 3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310798869.4A CN116785257B (en) | 2023-06-30 | 2023-06-30 | Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310798869.4A CN116785257B (en) | 2023-06-30 | 2023-06-30 | Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN116785257A CN116785257A (en) | 2023-09-22 |
| CN116785257B true CN116785257B (en) | 2026-02-03 |
Family
ID=88041484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310798869.4A Active CN116785257B (en) | 2023-06-30 | 2023-06-30 | Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116785257B (en) |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011097480A1 (en) * | 2010-02-05 | 2011-08-11 | University Of Louisville Research Foundation, Inc. | Exosomal compositions and methods for the treatment of disease |
| WO2012087241A1 (en) * | 2010-12-20 | 2012-06-28 | Agency For Science, Technology And Research | Method of purifying exosomes |
| CN110152015A (en) * | 2018-02-11 | 2019-08-23 | 上海市第六人民医院东院 | Human pluripotent stem cell exosomes loaded with anti-tumor drugs, preparation method and application thereof |
| WO2022268056A1 (en) * | 2021-06-22 | 2022-12-29 | 姜海涛 | Tissue-targeting exosomes and application thereof |
-
2023
- 2023-06-30 CN CN202310798869.4A patent/CN116785257B/en active Active
Non-Patent Citations (1)
| Title |
|---|
| 脐带间充质干细胞及其外泌体对宫颈癌HeLa细胞的作用初探;吕达;扬州大学学报;20200731;第41卷(第4期);54-58、70 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN116785257A (en) | 2023-09-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110123760B (en) | Preparation method of amorphous mesoporous manganese phosphate drug complex loaded with DNA topoisomerase Ⅱ inhibitor encapsulated by lipid membrane | |
| CN117100872B (en) | Nano delivery carrier for targeted tumor drug delivery and application thereof | |
| AboulFotouh et al. | Inhalable dry powders of microRNA-laden extracellular vesicles prepared by thin-film freeze-drying | |
| Mohaghegh et al. | Apigenin-loaded nanoparticles for obesity intervention through immunomodulation and adipocyte browning | |
| Huang et al. | Gas-injection of gold nanoparticles and anti-oxidants promotes diabetic wound healing | |
| Luo et al. | Adipose-derived mesenchymal stem cell exosomes ameliorate spinal cord injury in rats by activating the Nrf2/HO-1 pathway and regulating microglial polarization | |
| Huang et al. | In situ injectable hydrogel encapsulating Mn/NO-based immune nano-activator for prevention of postoperative tumor recurrence | |
| CN114452300B (en) | Application of black phosphorus nano-sheet in preparing anti-tumor chemotherapeutic drugs | |
| CN116785257B (en) | Complex of umbilical cord mesenchymal stem cell exosome and cisplatin, and preparation method and application thereof | |
| CN115089734B (en) | Carbonized MOFs nanoparticles loaded with phagocytosis-promoting peptides and preparation methods and applications in imaging and treatment of retinoblastoma | |
| WO2021223346A1 (en) | Application of yam protein extract in preparation of medication for treating erectile dysfunction | |
| CN116966134A (en) | The use of composite hydrogel loaded with shikonin and gold nanorods in suppressing immune cold triple-negative breast cancer | |
| Han et al. | FePt/MnO 2@ PEG nanoparticles as multifunctional radiosensitizers for enhancing ferroptosis and alleviating hypoxia in osteosarcoma therapy | |
| Wang et al. | Inhibitory role of cucurbitacin B with polylactic acid nanoparticles carrying long non-coding RNA (LncRNA) cancer susceptibility candidate 2c (CASC2c) in oral cancer cell migration and invasion through targeting of signal transcription and activator of transcription (STAT) signaling pathway | |
| CN119570710A (en) | Extraction method of seabuckthorn exosomes and its application in alleviating ulcerative bowel disease | |
| CN119405841A (en) | A preparation process and application of magnolol-loaded plant exosomes | |
| CN120078705A (en) | An exosome-coated responsive drug-loaded dendrimer nanogel system and its preparation method and application | |
| CN118976003A (en) | Exosomes loaded with salidroside and preparation method and application thereof | |
| Niu et al. | Manganese-based nanozymes as broad-spectrum antioxidants against cisplatin-induced skeletal muscle atrophy | |
| CN115969880A (en) | A kind of ferroptosis-immune combined therapy medicinal composition and preparation method thereof | |
| CN113181166A (en) | Application of curzerene alcohol in preparation of anti-lung cancer drugs and anti-lung cancer drugs | |
| CN115920074B (en) | Mesoporous silicon nano delivery carrier, medicine-carrying compound, preparation method and application | |
| CN118325814B (en) | Sophora japonica exosomes and their use in preparing drugs for treating digestive tract mucosal barrier damage | |
| CN118079072B (en) | Garlic source exosome particle wound dressing and preparation method and application thereof | |
| CN120392817A (en) | Application of ginsenoside Rb1 carbon nanodots in the preparation of pharmaceutical preparations for anti-tumor and/or inhibition of human gastric cancer cells |
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 | ||
| GR01 | Patent grant |