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Medicine conveying system formed by ligand polypeptide PH1 and application thereof

A technology of a delivery system and a drug-carrying system, applied in the field of targeted polypeptide liposome preparations, can solve the problems of easy recurrence and poor prognosis, and achieve the effects of inhibiting tumor recurrence, great medical practicability, and inhibiting tumor cell proliferation.

Active Publication Date: 2014-06-04
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the traditional drug treatment for tumor cells often has a poor prognosis and is prone to recurrence, which has an important role in the existence of tumor-associated macrophages.

Method used

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  • Medicine conveying system formed by ligand polypeptide PH1 and application thereof
  • Medicine conveying system formed by ligand polypeptide PH1 and application thereof
  • Medicine conveying system formed by ligand polypeptide PH1 and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Example 1. Synthesis of PH1 polypeptide lipid

[0048] Hydrogenated soybean phospholipids (HSPC) and 1,2-distearoylphosphatidylethanolamine 2000-maleate (DSPE-PEG2000-Mal) were purchased from NOF Corporation;

[0049] PH1 polypeptide was purchased from Shanghai Jier Biochemical and Biological Co., Ltd.; other reagents were purchased from China Sinopharm Chemical Reagent Company;

[0050] All-trans retinoic acid (ATRA) was purchased from American Sigma;

[0051] Step 1. Synthesis of PH1 polypeptide lipid (DSPE-PEG2000-Mal-PH1)

[0052] (1) Preparation of degassed HEPES solution: 50ml of ultra-pure H2O is heated and boiled for 10min, filled with N2 and then cooled, add 595.75mg of HEPES salt to obtain a concentration of 50mM, adjust the pH to 7.0 with 2mol / L NaOH, the whole process is N2 protected Store at 4℃ for later use;

[0053] (2) Weigh 10mg of DSPE-PEG2000-MAL powder, add 10ml of degassed HEPES salt to the hydrated lipid film to form a micellar solution; according to the pe...

Embodiment 2

[0061] Example 2. Preparation and identification of all-trans retinoic acid polypeptide liposome complex

[0062] Egg yolk lecithin (EPC) was purchased from Nippon Oil & Fat Co., Ltd., Lot No: 108057-3;

[0063] Cholesterol and PEGylated phospholipid 1,2-monostearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) were purchased from Avanti Polar Lipids, USA;

[0064] Step 1. Preparation of all-trans retinoic acid and polypeptide liposome complex

[0065] The lipid ratio of the eight liposome formulations (as shown in Table 2): egg yolk lecithin (EPC): cholesterol (Chol): polypeptide lipid: PEGylated phospholipid 1,2-monostearoyl phosphatidyl Ethanolamine-polyethylene glycol 2000 (DSPE-PEG2000);

[0066] Table 2

[0067] prescription Molar ratio of composition 2%PEG ATRA:EPC:CHOL:DSPE-PEG2000=3:15:10:0.52 4%PEG ATRA:EPC:CHOL:DSPE-PEG2000=3.3:15:10:1 NON-ATRA PH1:EPC:CHOL:DSPE-PEG2000=0.52:15:10:0.52 2%PH1+2%PEG ATRA:PH1:EPC:CHOL:DSPE-PEG2000=3.4:0.52:15:10:0.5...

Embodiment 3

[0079] Example 3. In vivo and in vitro binding test of polypeptide liposomes and tumor-associated macrophages (TAMs)

[0080] Egg yolk lecithin (EPC) was purchased from Nippon Oil & Fat Co., Ltd., Lot No: 108057-3;

[0081] Cholesterol and PEGylated phospholipid 1,2-monostearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) were purchased from Avanti Polar Lipids, USA;

[0082] Fluorescent lipid FITC DHPE was purchased from Invitrogen, USA

[0083] Polypeptide lipid (DSPE-PEG2000-maleimid-PH1) is synthesized by itself;

[0084] Anti-mouse FITC-CD11b antibody, Anti-mouse PE-Gr1 antibody, Anti-mouse Percp / cy5.5-F4 / 80 antibody, Anti-mouse FITC-CD11b antibody and its isotype control antibody were all purchased from ebiosciecce, USA;

[0085] Step 1: inoculate tumor

[0086] 1x106 4T-1 cells were trypsinized and resuspended in 200μL PBS buffer; 6-week-old Balb / c mice were injected with tumor cell suspension subcutaneously into the mammary glands; after 2 weeks, the tumor gre...

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Abstract

The invention relates to a medicine conveying system formed by ligand polypeptide PH1 and an application thereof. The medicine conveying system comprises a ligand polypeptide PH1, a medicine carrying system and at least one active substance, wherein the polypeptide PH1 is connected on the surface of the medicine carrying system. The invention also relates to the application of the ligand polypeptide PH1 in preparing a medicine capable of specifically binding tumor-related macrophage. Discovered and proved by long-time test, the polypeptide PH1 can well target tumor-related cells, induce the differentiation of the tumor-related cells and suppress the tumor growth; the composite of PH1 polypeptide lipidosome can well target the tumor-related macrophage and can be applied to target conveying of the tumor-related macrophage of small-molecular medicines and gene medicines. The medicine conveying system has the advantages that the transretinoic acid polypeptide lipidosome can induce the differentiation of the tumor-related macrophage and suppress the tumor growth effectively, and can be applied to inhibiting proliferation of the tumor cells and the neoplasm recurrence so as to have great medical practicability.

Description

Technical field [0001] The present invention relates to a targeting polypeptide liposome preparation and its application, in particular to a drug delivery system formed by a ligand polypeptide PH1 and its application. Background technique [0002] In many years of clinical practice, it has been observed that a large number of inflammatory cells infiltrate the tumor tissues of tumor patients, but its biological significance has only been paid attention to by the academic community in recent years: these tumor-related inflammatory cells are considered to be the growth of tumors. , Survival, and metastasis have an important role in promoting. [0003] The source of tumor-related inflammatory cells is thought to be Myeloid cells derived from bone marrow. In normal tissues, these myeloid-derived precursor cells can quickly differentiate into granulocytes, macrophages, and dendritic cells, but under disease conditions such as tumors, the differentiation of these precursor cells is inhib...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K31/203A61K9/127A61P35/00
Inventor 徐宇虹吴烈宜司晓菲
Owner SHANGHAI JIAO TONG UNIV
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