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Bionic nanocarrier for treating GBM (glioblastoma) and preparation method of bionic nanocarrier

A biomimetic nanotechnology, brain glioma technology, applied in the field of biomedical engineering, can solve the problems of less tumor accumulation, insufficient cell uptake, short half-life, etc., and achieve strong penetration ability, increased blood circulation time, and rapid charge conversion. Effect

Active Publication Date: 2019-06-18
HENAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, siRNA therapy for GBM is still limited by its extremely short half-life, poor blood-brain barrier penetration, low tumor accumulation, insufficient cellular uptake, and cumbersome endocytic pathways.

Method used

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  • Bionic nanocarrier for treating GBM (glioblastoma) and preparation method of bionic nanocarrier
  • Bionic nanocarrier for treating GBM (glioblastoma) and preparation method of bionic nanocarrier
  • Bionic nanocarrier for treating GBM (glioblastoma) and preparation method of bionic nanocarrier

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] This embodiment provides a method for preparing a biomimetic nanocarrier for the treatment of glioma, comprising the following steps:

[0065] 1. Preparation of citraconic anhydride (Citraconic Anhydride, CA) grafted polylysine (Poly lysine, PLL):

[0066] 1.1 Dissolve polylysine PLL in PBS buffer, slowly add citraconic anhydride;

[0067] 1.2 and adjust the pH value to neutral with NaOH;

[0068] 1.3 The mixture was stirred overnight at room temperature;

[0069] 1.4 Dialyze in water to remove unreacted citraconic anhydride, and dry to obtain citraconic anhydride grafted polylysine PLL-CA.

[0070] 2. Preparation of red blood cell membrane RBCm:

[0071] 2.1 Take the blood sample and centrifuge at 4°C for 300s to remove the plasma and buffy coat to obtain red blood cells;

[0072] 2.2 Wash the obtained red blood cells with cold 1×PBS buffer 3 times, and then treat them with hypotonic 0.25×PBS buffer on ice for 28 minutes;

[0073] 2.3 Centrifuge the solution in st...

Embodiment 2

[0087] This embodiment provides a method for preparing a biomimetic nanocarrier for the treatment of glioma, comprising the following steps:

[0088] 1. Preparation of citraconic anhydride (Citraconic Anhydride, CA) grafted polylysine (Poly lysine, PLL):

[0089] 1.1 Dissolve polylysine PLL in PBS buffer, slowly add citraconic anhydride;

[0090] 1.2 and adjust the pH value to neutral with NaOH;

[0091] 1.3 The mixture was stirred overnight at room temperature;

[0092] 1.4 Dialyze in water to remove unreacted citraconic anhydride, and dry to obtain citraconic anhydride grafted polylysine PLL-CA.

[0093] 2. Preparation of red blood cell membrane RBCm:

[0094] 2.1 Take the blood sample and centrifuge at 4°C for 300s to remove the plasma and buffy coat to obtain red blood cells;

[0095] 2.2 Wash the obtained red blood cells with cold 1×PBS buffer three times, and then treat them with hypotonic 0.25×PBS buffer on ice for 35 minutes;

[0096] 2.3 Centrifuge the solution i...

Embodiment 3

[0110] This embodiment provides a method for preparing a biomimetic nanocarrier for the treatment of glioma, comprising the following steps:

[0111] 1. Preparation of citraconic anhydride (Citraconic Anhydride, CA) grafted polylysine (Poly lysine, PLL):

[0112] 1.1 Dissolve polylysine PLL in PBS buffer, slowly add citraconic anhydride;

[0113] 1.2 and adjust the pH value to neutral with NaOH;

[0114] 1.3 The mixture was stirred overnight at room temperature;

[0115] 1.4 Dialyze in water to remove unreacted citraconic anhydride, and dry to obtain citraconic anhydride grafted polylysine PLL-CA.

[0116] 2. Preparation of red blood cell membrane RBCm:

[0117] 2.1 Take the blood sample and centrifuge at 4°C for 300s to remove the plasma and buffy coat to obtain red blood cells;

[0118] 2.2 Wash the obtained red blood cells with cold 1×PBS buffer three times, and then treat them with hypotonic 0.25×PBS buffer on ice for 35 minutes;

[0119] 2.3 Centrifuge the solution i...

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Abstract

The invention provides a bionic nanocarrier for treating GBM (glioblastoma) and a preparation method of the bionic nanocarrier and belongs to the field of biomedical engineering. According to the bionic nanocarrier for treating the GBM and the preparation method of the bionic nanocarrier, Ang-RBCm-CA / siRNA comprises Ang-RBCm (Ang (Angiopep-2) polypeptide modified red blood cell membrane) and citraconic anhydride grafted polylysine and polyethylenimine-siRNA compound (CA / siRNA). Ang-RBCm-CA / siRNA can effectively carry siRNA and protect siRNA against degradation. The Ang-RBCm-CA / siRNA has prolonged blood circulation time and high blood brain barrier penetrability, can be efficiently taken in by U87MG brain glial cells over-expressed by a low-density LPR (lipoprotein receptor) and can realizerapid charge conversion in endosome / lysosome, effectively release siRNA and effectively treat in-situ U87MG GBM.

Description

technical field [0001] The invention relates to the field of biomedical engineering, in particular to a bionic nano-carrier for treating glioma and a preparation method thereof. Background technique [0002] Glioma (GBM) is the most common and aggressive tumor in the central nervous system. Almost all drugs are ineffective in treating GBM patients due to their inability to penetrate the blood-brain barrier. In order to improve the blood-brain barrier penetration ability and the therapeutic effect of glioma, we have invested a lot of effort to design nanomedicines that can specifically target GBM cells and cross the blood-brain barrier. Studies have shown that low-density lipoprotein-related protein-1 (LRP-1), which is overexpressed on both endothelial cells and GBM cells of the blood-brain barrier, can undergo receptor-mediated transcytosis (RMT) and receptor-mediated endocytic mechanism to enhance blood-brain barrier penetration and tumor cell uptake. In recent years, ma...

Claims

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Application Information

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IPC IPC(8): A61K47/42A61K47/34A61K47/46A61K47/18A61K48/00A61K31/713A61P35/00
Inventor 师冰洋刘艳杰邹艳郑蒙
Owner HENAN UNIVERSITY
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