Microenvironment enzyme targeting combined antibody Fab cell targeting vector as well as preparation method and application thereof

A technology of cell targeting and microenvironment, applied in the field of biomedical engineering, can solve problems such as deficiency, achieve the effects of reducing tissue distribution and release, stabilizing structure, and maintaining stable circulation

Active Publication Date: 2022-04-22
中山大学南昌研究院
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In summary, there is currently a lack of nanocarrier systems that can effectively avoid non-specific drug absorpt

Method used

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  • Microenvironment enzyme targeting combined antibody Fab cell targeting vector as well as preparation method and application thereof
  • Microenvironment enzyme targeting combined antibody Fab cell targeting vector as well as preparation method and application thereof
  • Microenvironment enzyme targeting combined antibody Fab cell targeting vector as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Synthesis of S1, polyacetylimide grafted polyethylene glycol (PEG-PEI)

[0047] Polyethyleneimine-grafted polyethylene glycol (PEG-PEI) was synthesized by a two-step method. First, the terminal hydroxyl groups of monomethyl ether polyglycol were activated with carbonyldiimidazole, and then reacted with the amino groups of polyethyleneimine to generate PEG. -PEI. The specific operation is as follows: weigh monomethyl ether glycol (8.0 g, Mn=2 kDa) into a reaction flask, dry it in vacuum at 80° C. for 6 h, and add THF (60 mL) under an argon atmosphere to dissolve it. Weigh carbonyldiimidazole (CDI, 6.4g) and another reaction bottle, then slowly drop THF dissolved in mPEG-OH into the CDI bottle with a constant pressure dropping funnel, and stir the reaction overnight at room temperature. Distilled water (0.648 mL) was added to inactivate excess CDI, and stirring was continued for 30 min. Precipitate the solution into a large amount of cold ether, filter and dry in vacuo ...

Embodiment 2-4， comparative example 1-6

[0067] Compared with Example 1, Example 2-4 or Comparative Example 1-6 can be prepared by changing the dosage of polymer, drug and SPIO in Step S3 or omitting a certain step in Steps S3, S4, S5, S6, and S7 , see Table 1 below for details:

[0068] Table 1: Examples and comparative examples

[0069]

[0070]

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Abstract

The invention discloses a microenvironment enzyme targeting combined antibody Fab cell targeting vector and a preparation method and application thereof.The targeting vector is of a core-shell double-layer structure, and an enzyme substrate polypeptide-PEG modified lipid bimolecular membrane which is disintegrated in a targeted mode under the action of high-expression enzyme in contact with placenta tissue interstitial fluid serves as a shell; a drug carrier modified by a marker antibody with high specific expression on the surface of placental trophoblast is used as an inner core, and superparamagnetic ferroferric oxide SPIO nanoparticles, small molecule drugs for regulating and controlling the functions of the placental trophoblast, therapeutic genes or a combination of the superparamagnetic ferroferric oxide SPIO nanoparticles, the small molecule drugs and the therapeutic genes are loaded in the drug carrier. The targeting carrier disclosed by the invention can effectively avoid non-specific drug absorption of other organs outside the placenta of a maternal body and a fetus, so that delivery and function regulation and control of specific drugs of trophoblasts in the placenta are realized.

Description

technical field [0001] The invention relates to the field of biomedical engineering, in particular to a microenvironmental enzyme targeting combination antibody Fab cell targeting carrier and its preparation method and application. Background technique [0002] Adhesion placenta refers to the pathological state in which part or even the whole placental villous tissue abnormally invades the myometrium due to the loss of part or all of the decidua basal layer of the placenta. In severe cases, the placenta invades the deep myometrium of the uterus, or the placenta penetrates the uterine wall and reaches the uterine serosa or even invades adjacent organs. The clinical risk of this type of disease is extremely high, and the perinatal period often causes uncontrollable hemorrhage, often leading to hysterectomy and liver resection, which endangers the life safety of mother and child. Current studies have shown that previous cesarean section history, multiple abortion history, and ...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/42A61K47/68A61K47/69A61K31/7048A61K31/7088A61P15/00
CPCA61K9/127A61K47/42A61K47/6843A61K47/6935A61K31/7048A61K31/7088A61P15/00A61K2300/00Y02A50/30
Inventor 郭宇吴志强曹众姚清河赵子洲王伟伟郭若汨李庆玲
Owner 中山大学南昌研究院
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