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Fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as preparation method and application of fibrin gel

A fibrin gel, PD-L1 technology, applied in the field of medicine, to achieve the effect of preventing tumor recurrence

Pending Publication Date: 2022-04-12
SHENYANG PHARMA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] At present, platelet exosomes are mainly to explore their behavior in blood, and there is no use of platelet exosomes to encapsulate doxorubicin combined with PD-L1 monoclonal antibody to eliminate in situ tumors, inhibit distant tumors, and target capture and clear circulating tumor cells Related research and related reports

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  • Fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as preparation method and application of fibrin gel
  • Fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as preparation method and application of fibrin gel
  • Fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as preparation method and application of fibrin gel

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Experimental program
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Effect test

Embodiment 1

[0095] Preparation and characterization of platelet-encapsulated doxorubicin and bioreactive fibrin gels.

[0096] Synthesis schematic see figure 1 .

[0097] 1) Preparation of platelet exosomes.

[0098] After platelet-rich plasma was anticoagulated with EDTA, red blood cells were removed by centrifugation at 100g for 20 minutes, the supernatant was added to ACD solution to prevent platelet activation, and platelet membrane was prepared by centrifugation at 800g for 20 minutes. Tyrode-HEPES buffer (1mM MgCl 2 , 2mM CaCl 2 and 3mM KCl 2 ) to dilute platelets to 250×10 6 platelets / mL, and bound Ca 2+ ionophore (10 mM, Sigma-Aldrich), incubated for 30 minutes, and then centrifuged at 800 g for 10 minutes. The collected supernatant was further ultracentrifuged, and the extracellular vesicles were ultracentrifuged at 100,000 g for 90 minutes to concentrate the particles. After resuspension, the extracellular vesicles were passed through a 220nm microporous membrane to obta...

Embodiment 2

[0105] Adhesion of platelet exosomes to tumor cells.

[0106] We explored the adhesion between DiR-labeled Pex and B16-F10 cells by confocal laser scanning microscopy and observed the co-localization of DiR-labeled Pex and CD44 in B16-F10 cells ( image 3 D).

Embodiment 3

[0108] The uptake and cytotoxicity of PexD by B16-F10 cells.

[0109] We observed the cellular internalization of PexD by B16-F10 by confocal ( image 3 A), At the same incubation time, the cellular uptake efficiency of PexD is higher than that of free DOX, which may be due to the binding of Pex to B16-F10 cells. We further used flow cytometry to quantify the cellular uptake of PexD and free DOX solutions by B16-F10 cells. Such as image 3 As shown in B and 3C, PexD showed enhanced DOX uptake by B16-F10 cells compared to free DOX solution. These results are consistent with those observed by fluorescence microscopy.

[0110] The in vitro cytotoxicity of PexD and free DOX solutions on B16-F10 cells was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of. Compared with free DOX solution, PexD had significantly higher cytotoxicity ( Figure 10 ). After calculation, the half maximal inhibitory concentration (IC) of PexD 50 ) values...

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Abstract

The invention discloses fibrin gel containing adriamycin-entrapped platelet exosome and PD-L1 monoclonal antibody as well as a preparation method and application thereof, and belongs to the technical field of medicines, and compared with an adriamycin solution, the adriamycin-entrapped platelet exosome can be better combined with tumor cells, induce death of immunogenic tumor cells and promote anti-tumor immune response. Meanwhile, the blood platelet exosome loaded with adriamycin can enter blood circulation through damaged blood vessels, and tumor cells in circulation are tracked and removed. The aPD-L1 is released at the tumor site at the same time, so that a PD-1 / PD-L1 pathway can be blocked, and the tumor killing effect of cytotoxic T cells is recovered. The combination of the two strategies can trigger stronger T cell immune response, and obviously improves the tumor immune microenvironment. The method provided by the invention provides a new strategy and more choices for the combination of chemotherapy and immunotherapy, and meets the urgent demand on efficient preparations in clinic.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to a fibrin gel containing platelet exosomes loaded with doxorubicin and a PD-L1 monoclonal antibody, a preparation method thereof, and an application in the preparation of drugs for treating tumor metastases. Background technique [0002] Surgery is an effective method for the treatment of melanoma, but unfortunately, local residual tumor microinfiltration and systemic CTCs continue to cause tumor recurrence, resulting in patient death. Immune checkpoint inhibitors, particularly PD-L1 monoclonal antibodies, have improved the efficacy of melanoma therapy and produced durable clinical responses in some patients. However, systemic administration of immune checkpoint inhibitors promotes sustained clinical responses in less than 20% of patients with immunogenic tumors. Due to the lack of immunogenic antigens and various immune resistance mechanisms, the clinical efficacy of...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/46A61K39/395A61K31/704A61K9/06A61K47/42A61P35/04A61P35/00
Inventor 孙进赵健叶皓何仲贵
Owner SHENYANG PHARMA UNIVERSITY
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