CN-121987631-A - Apatinib-immune synergistic nano-drug based on mycogenic vesicles and preparation method and application thereof

Abstract

The invention discloses an apatinib-immune synergistic nano-drug based on bacterial source vesicles, a preparation method and application thereof, wherein the nano-drug is Apatinib-MVs, membrane vesicles secreted by parabacteroides guli are used as carriers for encapsulating an anti-angiogenesis drug apatinib, and in-vitro anti-tumor experimental results show that the nano-drug can play a high-efficiency anti-tumor effect through a dual synergistic mechanism for simultaneously inhibiting tumor angiogenesis and activating anti-tumor immune response.

Inventors

• DUAN XIANGGUO
• SU CHUNXIA
• YANG XIAOJUAN
• LIU JIAYU

Assignees

• 宁夏医科大学

Dates

Publication Date

20260508

Application Date

20260123

Claims (7)

1. 1. The apatinib-immune synergistic nano-drug based on fungus source vesicles is characterized in that the nano-drug takes outer membrane vesicles secreted by parabacteroides guli as carriers, and the inside of the vesicles is coated with an anti-angiogenesis drug apatinib.
2. 2. The nano-drug according to claim 1, wherein the mass ratio of apatinib to outer membrane vesicles is 2:1.
3. 3. The nano-drug according to claim 1, wherein the encapsulation efficiency of apatinib is up to 68.5% and the drug loading is 9.2%.
4. 4. A method for preparing a nano-drug according to any one of claims 1 to 3, comprising the steps of culturing Paramycolatopsis Gu under anaerobic conditions for 48 to 72 hours, collecting culture supernatant, purifying by ultracentrifugation to obtain outer membrane vesicles, incubating apatinib and the outer membrane vesicles at 37 ℃ for 12 hours in a dark place, and dialyzing to remove unencapsulated free drug, thus obtaining the nano-drug Apatinib-MVs.
5. 5. Use of a nano-drug according to any one of claims 1-3 for the preparation of a medicament for the treatment of breast cancer.
6. 6. The use according to claim 5, wherein the nano-drug is capable of exerting a highly potent anti-tumor effect by a dual synergistic mechanism of inhibiting tumor angiogenesis and activating an anti-tumor immune response.
7. 7. The use of claim 5, wherein the nanomedicine comprises a pharmaceutically acceptable excipient comprising one or more of a diluent, a stabilizer, a buffer, a preservative, or a carrier.

Description

Apatinib-immune synergistic nano-drug based on mycogenic vesicles and preparation method and application thereof Technical Field The invention belongs to the technical field of biological medicines and nano medicines, and particularly relates to an apatinib-immune synergistic nano medicine based on fungus source vesicles, and a preparation method and application of the nano medicine. Background Breast cancer is one of the most common malignant tumors of women worldwide, the treatment strategies of the breast cancer comprise operation, radiotherapy, chemotherapy, targeted therapy, immunotherapy and the like, the anti-angiogenesis drug apatinib (Apatinib) is a vascular endothelial growth factor receptor-2 (VEGFR-2) inhibitor with high selectivity, and can inhibit tumor growth and metastasis by blocking tumor angiogenesis, however, the apatinib has the problems of easy drug resistance, toxic side effects and the like. The nano drug delivery system provides an effective means for improving drug targeting and reducing toxic and side effects, the bacterial membrane vesicles (Membrane Vesicles, MVs) are novel biological nano carriers, have the advantages of good biocompatibility, easiness in modification, capability of naturally targeting tumors and activating immune response and the like, and the parabacteroides gulani (Parabacteroides goldsteinii) is used as an intestinal probiotics, has high safety of the membrane vesicles from which the parabacteroides gullies, has unique immune regulation characteristics and is an ideal drug delivery platform. At present, no report on the fact that the Paenibacillus archaea membrane vesicles are used as carriers to encapsulate the Apatinib for the cooperative treatment of the breast cancer exists. Disclosure of Invention The invention aims to overcome the defects of the prior art and provide an apatinib-immune synergistic nano-drug (Apatinib-MVs) based on fungus source vesicles, which can play a double role of anti-angiogenesis and immune activation and realize high-efficiency synergistic treatment on breast cancer. Another object of the present invention is to provide a method for preparing the above nano-drug. It is a further object of the present invention to provide the use of the above nano-drug. The apatinib-immune synergistic nano-drug based on fungus source vesicles takes outer membrane vesicles secreted by parabacteroides archaea as carriers, and the inside of the vesicles is coated with an anti-angiogenesis drug apatinib. Preferably, the mass ratio of the apatinib to the outer membrane vesicles of the nano-drug is 2:1. Preferably, the encapsulation rate of the apatinib of the nano-drug in the outer membrane vesicle reaches 68.5%, and the drug loading rate is 9.2%. A preparation method of the apatinib-immune synergistic nano-drug based on fungus source vesicles comprises the following steps of firstly culturing Paecilomyces griseus under anaerobic conditions for 48-72 hours, collecting culture supernatant, performing ultracentrifugation purification to obtain outer membrane vesicles, then incubating the apatinib and the outer membrane vesicles for 12 hours at 37 ℃ in a dark place, and dialyzing to remove unencapsulated free drugs, thus obtaining the nano-drug Apatinib-MVs. An application of apatinib-immune synergistic nano-drug based on fungus-derived vesicles in preparing a drug for treating breast cancer. Preferably, the nano-drug can exert a high-efficiency anti-tumor effect through a dual synergistic mechanism of inhibiting tumor angiogenesis and activating an anti-tumor immune response. Preferably, the nanomedicine includes a pharmaceutically acceptable excipient that includes one or more of a diluent, stabilizer, buffer, preservative, or carrier. The apatinib-immune synergistic nano-drug based on the bacteria source vesicle can achieve the following beneficial effects that (1) intelligent targeting delivery is achieved, the Paenibacillus archaea outer membrane vesicle has natural tumor targeting and a certain immune adjuvant effect, enrichment of the drug at a tumor part can be improved, and (2) the preparation is simple and convenient, the biological safety is high, the preparation method is mild in condition and clear in step, and the outer membrane vesicle from the probiotics is taken as a carrier, so that the biocompatibility is good, and the potential toxicity is low. Other features of the present invention and its advantages will become apparent from the following detailed description of exemplary embodiments of the invention, which proceeds with reference to the accompanying drawings. Drawings The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description, serve to explain the principles of the invention. FIG. 1 is a flow chart of a nano-drug preparation process provided by an embodiment of the application; FIG. 2 is a graph of physicochemical cha