MMP enzyme sensitive placenta microenvironment and tumor microenvironment targeting vector as well as preparation method and application thereof

A tumor microenvironment and microenvironment technology, applied in the field of biomedical engineering, can solve problems such as lack, achieve the effects of reducing tissue distribution and release, maintaining stable circulation, and reducing drug leakage

Pending 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

[0009]In summary, there is currently a lack of nanocarriers that can effectively avoid non-specific drug absorption by mothers and fetuses, and then achieve specific drug delivery and functional regulation of TB cells in the placenta system

Method used

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  • MMP enzyme sensitive placenta microenvironment and tumor microenvironment targeting vector as well as preparation method and application thereof
  • MMP enzyme sensitive placenta microenvironment and tumor microenvironment targeting vector as well as preparation method and application thereof
  • MMP enzyme sensitive placenta microenvironment and tumor microenvironment targeting vector as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Synthesis of S1, polyacetylimide grafted polyethylene glycol (PEG-PEI)

[0050] 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

[0071] 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:

[0072] Table 1: Examples and comparative examples

[0073]

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Abstract

The invention discloses an MMP enzyme sensitive placenta microenvironment and tumor microenvironment 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 placental trophoblast surface specificity high expression marker antibody modified drug carrier is used as an inner core, and the drug carrier is a copolymer formed by a polyethylene glycol modified polycation carrier and hydrophobic degradable polyester. The MMP enzyme sensitive placenta microenvironment and tumor microenvironment targeting carrier can effectively avoid non-specific drug absorption of other organs outside a maternal placenta and a fetus, so that delivery and function regulation of specific drugs of lesion trophoblast cells in the placenta are realized.

Description

technical field [0001] The invention relates to the field of biomedical engineering, in particular to an MMP enzyme-sensitive placental microenvironment and tumor microenvironment targeting carrier and its preparation method and application. Background technique [0002] Gestational trophoblastic neoplasms (GTN) include invasive mole, choriocarcinoma, placental site trophoblastic neoplasm, and epithelioid trophoblastic neoplasm. Most GTN with onset after pregnancy responds well to chemotherapy, and the effective rate of chemotherapy can reach more than 90%. However, among the GTNs, the most difficult type to manage is a pregnancy-associated trophoblastic tumor arising in the placenta of a pregnant woman. This type of tumor develops during pregnancy and coexists with the fetus and placenta. The main pathological feature is that the tumor occurs in the placenta, and the tumor can be confined to the uterus, or protrude into the uterine cavity as a polyp, or invade the muscle l...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K41/00A61K45/06A61K47/64A61K47/68A61K31/715A61P35/00B82Y5/00
CPCA61K47/6935A61K41/00A61K45/06A61K47/6849A61K47/6851A61K47/64B82Y5/00A61K47/6911A61K31/715A61P35/00
Inventor 郭宇
Owner 中山大学南昌研究院
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