Live cell drug delivery system based on macrophages, and preparation method and application thereof

A technology of macrophages and drug-carrying systems, applied in cell culture active agents, biochemical equipment and methods, animal cells, etc., can solve the problems of small diameter of tumor metastases, difficulty in ensuring therapeutic effect, and high dispersion, and achieve good results Therapeutic effect, maintaining stability, maintaining active effect

Active Publication Date: 2019-11-29
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the small diameter and high dispersion of tumor metastases, simple passive targeting is difficult to ensure a good therapeutic effect. Therefore, the development of efficient nano-drug delivery system is still a challenging problem.

Method used

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  • Live cell drug delivery system based on macrophages, and preparation method and application thereof
  • Live cell drug delivery system based on macrophages, and preparation method and application thereof
  • Live cell drug delivery system based on macrophages, and preparation method and application thereof

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preparation Embodiment 1

[0052] In this example, a living cell drug delivery system based on M2 macrophages was obtained by inducing reassembly of macrophages in vitro. Specifically, the preparation method of the living cell drug delivery system based on M2 type macrophages comprises the following steps:

[0053] (1) Synthesis of dimyristoylphosphatidylethanolamine-pegylated maytansine-4 and dimyristoylphosphatidylethanolamine-pegylated bee venom polypeptide propeptide

[0054] 1) Synthesis of Disulfide-Linked Dimyristoyl Phosphatidylethanolamine-PEGylated Maytansine-4

[0055] Disulfide-linked dimyristoylphosphatidylethanolamine-PEGylated maytansine-4 was synthesized in two steps: ① 3-(2-pyridyldimercapto)propionic acid N-hydroxysuccinimidyl ester-maytansine The synthetic route of prime-4 is shown in Figure 2(A). The specific steps are as follows: weigh maytansine-4 (19.5 mg, 0.025 mmol, purchased from Suzhou Borui Biological Co., Ltd.) and dissolve it in 1 mL of methanol solution, weigh 3-(2-pyrid...

preparation Embodiment 2

[0084] In this example, a living cell drug delivery system based on M1 macrophages was obtained by inducing macrophages in vitro. Specifically, the preparation method of the living cell drug delivery system based on M1 type macrophages includes the following steps: (1) Isolation and purification of mouse bone marrow-derived macrophages

[0085] 1) Take mouse bone marrow cells (Balb / c-nu nude mice (purchased from Shanghai Experimental Animal Center, Chinese Academy of Sciences)), and culture them in RPMI 1640 (Gibco) medium containing 10% fetal bovine serum (Gibco). Add recombinant mouse macrophage colony-stimulating factor (M-CSF, purchased from Sigma, with a final concentration of 20ng / mL) and LPS (20ng / mL) in the culture medium, and place on a low-adhesion plate (purchased from Corning ), 37°C, 5% CO 2 After culturing for 5 days, adherent cells were obtained.

[0086] 2) Replace the medium of M1 macrophages, and add dimyristoylphosphatidylethanolamine (DMPE)-pegylated mayt...

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Abstract

The invention discloses a living cell drug delivery system based on macrophages, and a preparation method and application thereof. The living cell drug delivery system based on macrophages comprises macrophages, anchored chemotherapeutic drugs and anchored cell lysis-promoting groups. The preparation method comprises the following steps: taking mouse bone marrow cells, culturing in vitro, adding arecombinant mouse macrophage colony stimulating factor and a mouse breast cancer 4T1 cell culture supernatant or lipopolysaccharide LPS into a culture medium, continuously culturing, and inducing macrophage polarization to obtain regulatory M1 or M2 macrophages; and jointly incubating the anchored chemotherapeutic drug and the anchored cell lysis-promoting group in the macrophage culture medium to prepare the macrophage-based living cell drug delivery system. The prepared living cell drug delivery system based on macrophages can be actively targeted to the lung metastasis focus of breast cancer, and lung metastasis of breast cancer is effectively inhibited.

Description

technical field [0001] The invention belongs to the field of pharmacy, and in particular relates to a living cell drug delivery system based on macrophages, its preparation method and application. Background technique [0002] Breast cancer metastasis is the main cause of death in breast cancer patients. In the early stage of breast cancer, surgical resection can be used for treatment, but surgical resection is difficult to completely remove the lesion, and the prognosis is poor, and it is easy to relapse and metastasis. Chemotherapeutic drugs can inhibit the proliferation and spread of breast cancer cells, but due to poor selectivity of chemotherapeutic drugs, they usually have serious side effects, and after chemotherapy, it is easy to cause breast cancer tumor cells to develop drug resistance, which leads to the failure of clinical treatment. Radiation therapy can kill tumor cells, but the normal cells adjacent to the tumor will also be damaged to varying degrees, and it...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K45/00A61P35/04C12N5/0786
CPCA61K45/00A61K47/6901A61P35/04C12N5/0645C12N2501/052C12N2501/22
Inventor 李亚平张志文曹海强王洪
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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