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A mr imaging polymer micelle for transporting antibodies for tumor immunotherapy and its preparation method

A polymer glue, immunotherapy technology, applied in the field of polymer chemistry and biomedical engineering, can solve problems such as adverse reactions

Active Publication Date: 2021-03-26
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, immune checkpoint inhibitor antibody therapy is prone to immune-related adverse reactions, such as myocarditis, hepatitis, pneumonia, dermatitis, etc., which are considered to be caused by abnormal activation of autoreactive T cells

Method used

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  • A mr imaging polymer micelle for transporting antibodies for tumor immunotherapy and its preparation method
  • A mr imaging polymer micelle for transporting antibodies for tumor immunotherapy and its preparation method
  • A mr imaging polymer micelle for transporting antibodies for tumor immunotherapy and its preparation method

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Experimental program
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Embodiment 1

[0033] A method for preparing an MR imaging polymer micelle for delivering antibodies for tumor immunotherapy, comprising the following steps:

[0034] Synthesis of S1.L-Phe-NCA (L-phenylalanine-cyclocarbonic anhydride) polymer: the specific synthesis steps are as follows: Weigh 10g of L-phenylalanine in a 500mL three-neck flask, add freshly steamed 100mL Ethyl acetate, after heating to reflux at 90°C, drop into 50 mL of ethyl acetate dissolved with 10 g of triphosgene, stir, and heat to reflux for about 5 hours until the solution becomes a yellow clear solution. After returning to room temperature, freeze at -40°C for 0.5h. The ethyl acetate layer was pre-cooled with 4°C saturated NaHCO 3 solution (100 mL×2), saturated NaCl solution (50 mL×2), and separated. The ethyl acetate layer was washed with MgSO 4 Dry, filter, concentrate by rotary evaporation, precipitate in freshly steamed petroleum ether, filter with suction, recrystallize the solid obtained with ethyl acetate / pe...

Embodiment 2

[0054] A method for preparing an MR imaging polymer micelle for delivering antibodies for tumor immunotherapy, comprising the following steps:

[0055] Steps S1 to S3, and S5 to S6 are the same as in Embodiment 1

[0056] S4. Preparation of micelles loaded with SPIONs: 8 mg SPION, 30 mg N 3 - PEG-PLPhe was dissolved in 10mL THF, added dropwise to 30mL deionized water under ultrasonication, dialyzed with water to remove THF (dialysis bag MWCO 14k), filtered with a 450nm water phase filter, and ultra-high-speed centrifuged at 50k rpm to remove unwrapped SPIONs The micelles were reconstituted with 5mM PBS (pH 7.4) to about 2.5mg / mL. The mass of superparamagnetic Fe3O4 nanoparticles (SPIONs) accounted for 25% of the mass of polymer micelles. The preparation method adopts conventional techniques in this technical field.

Embodiment 3

[0058] A method for preparing an MR imaging polymer micelle for delivering antibodies for tumor immunotherapy, comprising the following steps:

[0059] Steps S1 to S3, and S5 to S6 are the same as in Embodiment 1

[0060] S4. Preparation of micelles loaded with SPIONs: mix 4mg SPION, 32mg N 3 - PEG-PLPhe was dissolved in 5mL THF, added dropwise to 25mL deionized water under ultrasonication, dialyzed with water to remove THF (dialysis bag MWCO14k), filtered with a 450nm water phase filter head, and ultra-high-speed centrifuged at 60k rpm to remove the glue that did not wrap SPIONs Reconstitute with 5mM PBS (pH 7.4) to about 2.5mg / mL. The mass of superparamagnetic Fe3O4 nanoparticles (SPIONs) accounted for 15% of the mass of polymer micelles. The preparation method adopts conventional techniques in this technical field.

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Abstract

The present invention discloses an MR imaging polymer micelle for transporting antibody for tumor immunotherapy, and a preparation method thereof. The polymer micelle has a core-shell structure, wherein superparamagnetic ferroferric oxide nanoparticles are loaded on the core, a matrix metalloproteinase-sensitive polypeptide conjugated antibody is formed the shell layer on the surface of the micelle, and a monomethyl ether polyethylene glycol mPEG20k conjugated with an acid sensitive bond is used as the shielding layer of the antibody. According to the present invention, when the polymer micelle reaches the tumor microenvironment (the pH value is less than or equal to 6.5), the shielding layer sheds, the antibody epitope is exposed, and the conjugated antibody is released under the action of the matrix metalloproteinase so as to achieve the controlled release of the antibody; and the polymer micelle can further achieve the integration of magnetic resonance (MR) imaging and tumor immunotherapy.

Description

technical field [0001] The invention belongs to the field of polymer chemistry and biomedical engineering, and more specifically relates to an MR imaging polymer micelle for transporting antibodies for tumor immunotherapy and a preparation method thereof. Background technique [0002] Malignant tumors seriously endanger human health. At present, the commonly used methods for treating cancer include surgery, radiotherapy, chemotherapy and immunotherapy. Tumor immunotherapy has become another effective therapy for tumor control after surgery, radiotherapy and chemotherapy, and is widely used in clinic. Among them, immune checkpoint inhibitor antibody therapy has attracted extensive attention because it has shown good anti-tumor activity in various tumors and significantly prolonged clinical survival. However, immune checkpoint inhibitor antibody therapy is prone to immune-related adverse reactions, such as myocarditis, hepatitis, pneumonia, dermatitis, etc., which are conside...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/69A61K47/65A61K47/60A61K39/395A61K49/12A61K49/18A61P35/00
CPCA61K49/126A61K49/1809C07K16/2818
Inventor 帅心涛徐永敏黄金生程度
Owner SUN YAT SEN UNIV
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