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Cell surface marker antibody Fab segment modified small molecule drug/therapeutic gene delivery system, preparation method and application

A cell surface and gene delivery technology, applied in the field of biomedical engineering, can solve problems such as deficiency, achieve the effect of reducing tissue distribution and release, maintaining stable circulation, and stable structure

Pending Publication Date: 2022-04-15
中山大学南昌研究院
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] In summary, there is currently a lack of nanocarrier systems that can effectively avoid non-specific drug absorption by the mother and fetus, and then achieve specific drug delivery and functional regulation of TB cells in the placenta

Method used

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  • Cell surface marker antibody Fab segment modified small molecule drug/therapeutic gene delivery system, preparation method and application
  • Cell surface marker antibody Fab segment modified small molecule drug/therapeutic gene delivery system, preparation method and application
  • Cell surface marker antibody Fab segment modified small molecule drug/therapeutic gene delivery system, preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Synthesis of S1, polyacetylimide grafted polyethylene glycol (PEG-PEI)

[0046] 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) in a reaction flask, dry it in vacuum at 80° C. for 6 h, 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 at room temperature overnight. Distilled water (0.648 mL) was added to inactivate excess CDI and stirring was continued for 30 min. The solution was precipitated into a large amount of cold diethyl ether, and vacuum-dried...

Embodiment 2-4， comparative example 1-6

[0066] Compared with Example 1, changing the dosage of polymer, drug and SPIO in step S3 or omitting a certain step in steps S3, S4, S5, S6, S7 can prepare Example 2-4 or Comparative Example 1-6 , see Table 1 below for details:

[0067] Table 1: Examples and comparative examples

[0068]

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Abstract

The invention discloses a cell surface marker antibody Fab segment modified small molecule drug / therapeutic gene delivery system and a preparation method and application thereof, and the delivery system comprises a lipid bimolecular membrane and a drug carrier, the lipid bimolecular membrane is modified by an enzyme substrate polypeptide-PEG which is disintegrated in a targeted manner under the action of an enzyme which is in contact with placenta tissue interstitial fluid and is highly expressed, and the drug carrier is modified by a marker antibody which is specifically and highly expressed on the surface of placenta trophoblasts; the drug carrier is loaded with superparamagnetic ferroferric oxide SPIO nanoparticles, a small molecule drug for regulating and controlling the placental trophoblast function, a therapeutic gene or a combination thereof. The delivery system disclosed by the invention can effectively avoid non-specific drug absorption of other organs outside the placenta of the maternal body and a fetus, so that delivery and function regulation and control of a trophoblast specific drug in the placenta are realized.

Description

technical field [0001] The invention relates to the field of biomedical engineering, in particular to a small molecule drug / therapeutic gene delivery system modified by the Fab segment of a cell surface marker antibody and its preparation method and application. Background technique [0002] Gestational diabetes mellitus (GDM) is the most common pregnancy complication, which can easily cause adverse pregnancy outcomes such as fetal growth restriction, macrosomia, neonatal respiratory distress syndrome, stillbirth, miscarriage and eclampsia. More importantly, GDM not only increases the adverse outcomes during pregnancy and perinatal period, but also has a profound impact on the two generations of mother and child in the long term after delivery. The lifelong glucose and lipid metabolism and obesity outcomes of mothers and offspring are also continuously and linearly correlated with mothers’ blood sugar during pregnancy, that is, the higher the mother’s blood sugar during preg...

Claims

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Application Information

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IPC IPC(8): A61K47/62A61K47/68A61K47/69A61K31/593A61K31/713A61K47/02A61K47/34A61P3/10B82Y5/00
Inventor 郭宇郭若汨姚清河李文滨曹众吴志强王伟伟李庆玲梁莹孙美丽陈珺逸
Owner 中山大学南昌研究院
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