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Nano immunoregulation medicine for regulating and controlling ratio of Treg/Th17 cells in focus microenvironment as well as preparation method and application of nano immunoregulation medicine

A technology of immune regulation and microenvironment, applied in the fields of biomedical engineering and chemistry, can solve the problems of lack of non-specific drug absorption, etc., and achieve the effects of promoting proportional changes and immune activity, reducing symptoms and improving prognosis

Pending Publication Date: 2022-04-08
THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] In summary, there is currently a lack of nanocarrier systems that can effectively avoid non-specific drug absorption from mothers and fetuses, and then achieve specific drug delivery and functional regulation of Treg cells and Th17 cells in the placenta

Method used

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  • Nano immunoregulation medicine for regulating and controlling ratio of Treg/Th17 cells in focus microenvironment as well as preparation method and application of nano immunoregulation medicine
  • Nano immunoregulation medicine for regulating and controlling ratio of Treg/Th17 cells in focus microenvironment as well as preparation method and application of nano immunoregulation medicine
  • Nano immunoregulation medicine for regulating and controlling ratio of Treg/Th17 cells in focus microenvironment as well as preparation method and application of nano immunoregulation medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Synthesis of S1, polyacetylimide grafted polyethylene glycol (PEG-PEI)

[0055] 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

[0076] 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:

[0077] Table 1: Examples and comparative examples

[0078]

[0079]

[0080] Functional evaluation experiment

[0081] 1. Nuclear magnetic resonance (MRI) experiments to evaluate the placenta-specific delivery function of drugs

[0082] Model building:

[0083] Female CBA / J mice and male DBA / 2 mice were mated in the same cage at a ratio of 2:1 during the estrus period, and the vaginal secretions smears of the female mice were stained with Papanicolaou on the second day, and the specimen vaginas were observed under an optical microscope Those with positive sperm were diagnosed as pregnant and marked as the 0th day of pregnancy (D0). A mouse model of recurrent abortion was established. Female CBA / J mice were mated with male BALB / C m...

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Abstract

The invention discloses a nano immunoregulation medicine for regulating and controlling the ratio of Treg / Th17 cells in a focus microenvironment and a preparation method and application of the nano immunoregulation medicine. The preparation method comprises the following steps: taking an enzyme substrate polypeptide-PEG modified lipid bimolecular membrane which is subjected to targeted disintegration under the action of an enzyme which is in contact with placenta tissue interstitial fluid and is highly expressed as a shell; a drug carrier modified by surface specific high-expression marker antibodies of important immunomodulatory cells (Treg cells and Th17 cells) of a placenta is used as an inner core, and superparamagnetic ferroferric oxide SPIO nanoparticles, a small molecule drug for regulating functions of the Treg cells and the Th17 cells of the placenta, a therapeutic gene or a combination thereof are loaded in the drug carrier. The nano immunoregulation medicine for regulating and controlling the ratio of the Treg cells to the Th17 cells in the microenvironment of the focus can effectively avoid non-specific medicine absorption of other organs outside the placenta of a maternal body and a fetus, and then delivery and function regulation and control of specific medicines of the Treg cells and the Th17 cells in the placenta are achieved.

Description

technical field [0001] The invention relates to the fields of chemistry and biomedical engineering, in particular to a nano-immune regulation drug for regulating the ratio of Treg / Th17 cells in the microenvironment of a lesion, a preparation method and application thereof. Background technique [0002] Recurrent spontaneous abortion (RSA) refers to 3 or more consecutive spontaneous abortions with the same spouse. It is a very common pregnancy complication with an incidence rate as high as 5%. RSA patients have a high risk of miscarriage in re-pregnancy, especially for those who have suffered three consecutive miscarriages, the recurrence risk is as high as 70% to 80%, which seriously affects the physical and mental health of patients. The etiology of RSA is complex. In the past, half or more of RSA patients were considered to be related to prethrombotic state during pregnancy, abnormal anatomical structure of female reproductive tract, abnormal endocrine function, chromosoma...

Claims

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Application Information

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IPC IPC(8): A61K9/127A61K47/42A61K47/34A61K47/68A61K31/573A61K31/713A61K48/00A61K41/00A61P15/06A61P37/02
Inventor 郭宇
Owner THE FIRST AFFILIATED HOSPITAL OF SUN YAT SEN UNIV
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