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Polypeptide self-assembled nano-drug as well as preparation method and application thereof

A nano-drug and self-assembly technology, which is applied in the preparation method of peptides, nano-drugs, nanotechnology, etc., can solve the problems of fast metabolism, short half-life of polypeptide hormones, low bioavailability, etc., to achieve improved half-life, strong hydrophobicity, Improve the effect of microenvironment

Pending Publication Date: 2022-04-15
ZHENGZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the presence of polypeptide enzymes, the half-life of polypeptide hormones is usually short, the metabolism is fast, and the bioavailability is relatively low

Method used

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  • Polypeptide self-assembled nano-drug as well as preparation method and application thereof
  • Polypeptide self-assembled nano-drug as well as preparation method and application thereof
  • Polypeptide self-assembled nano-drug as well as preparation method and application thereof

Examples

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preparation example Construction

[0048] Based on the same inventive concept, the present invention also provides a preparation method of polypeptide self-assembled nanomedicine, the preparation method comprising:

[0049] dissolving the amphiphilic molecule in the organic phase;

[0050] Under ultrasonic conditions, the organic phase dissolved with amphiphilic molecules is dispersed in the water phase, and left to stand to obtain polypeptide self-assembled nanomedicine.

[0051] In this application, the self-assembly process of polypeptide self-assembled nano-medicine is simple, self-assembled through weak intermolecular interactions (hydrophobic interactions) to form uniform and stable nanoparticles, no covalent bond is generated, and there is no reverse reaction, the prepared nano-medicine Good biocompatibility and enzyme responsiveness.

[0052] Further, the organic phase includes dimethyl sulfoxide, and the aqueous phase includes deionized water or phosphate buffer with a pH of 7.4.

[0053] In this app...

Embodiment 1

[0063] In this example, the nanomedicine was prepared by the following method: dissolving the amphiphilic molecule (with C18 at the hydrophobic end) in 10 μL of dimethyl sulfoxide (DMSO), and dissolving the amphiphilic molecule under 120W ultrasonic conditions The dimethyl sulfoxide solution was slowly dispersed in 1 mL of deionized water, ultrasonicated for 20 minutes, and left to stand at room temperature for 1 hour. The morphology and particle size of the obtained nanomedicine (named CAD) were characterized by transmission electron microscopy and laser particle size analyzer. The result is as figure 1 A and figure 2 shown. figure 1 A is the electron micrograph of the nano-medicine. It can be seen from the figure that the prepared nano-medicine is spherical and the particle size is relatively uniform. figure 2 For the particle size distribution and potential change of the nano-medicine in serum, the particle size distribution of the obtained nano-medicine is 30-40nm, and...

Embodiment 2

[0066] The purpose of this example is to determine the enzyme response of nanomedicine in pod protease solution.

[0067] The enzyme responsiveness was reflected by the morphology change after enzyme treatment. The nanomedicine obtained in Example 1 was dissolved in 1 ml of a buffer solution (pH 5.5) containing pod protease. Place in a constant temperature shaker at 37°C, incubate for more than two hours, take samples, and use transmission electron microscopy to characterize the nano-medicine after enzyme incubation, as shown in image 3 As shown, after the nanomedicine was treated with enzymes, the nanoparticles disintegrated and lost their spherical structure, reflecting the responsiveness of nanomedicines to enzymes.

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Abstract

The invention provides a polypeptide self-assembled nano-drug, and belongs to the technical field of polypeptide nano-materials, the nano-drug comprises spherical nano-particles formed by self-assembling amphiphilic molecules, the amphiphilic molecules comprise hydrophilic ends and hydrophobic ends, the hydrophilic end is formed by sequentially connecting a D-type polypeptide antagonist, a response polypeptide, an anti-angiogenesis polypeptide and a connecting peptide through covalent bonds, and the hydrophobic end comprises straight-chain fatty acid and is connected to the N end of the connecting peptide through a covalent bond. The nano-drug can realize efficient enrichment and long-acting retention at a tumor site, and the nano-drug can be responsively cut at a tumor local part with high expression of pod protease to release anti-vascular polypeptide and D-type polypeptide antagonist, so that the tumor immunosuppression microenvironment is improved while the angiogenesis at the tumor site is inhibited, and the tumor immunosuppression effect is improved. And postoperative recurrence and metastasis of tumors are prevented. The invention also provides a preparation method and application of the polypeptide self-assembled nano-drug.

Description

technical field [0001] The invention belongs to the technical field of polypeptide nanomaterials, in particular to a polypeptide self-assembled nanomedicine and its preparation method and application. Background technique [0002] According to the statistics of the World Health Organization (WHO) in 2020, cancer has caused a huge disease burden. It is not only one of the leading causes of death in the world, but also an important factor hindering the extension of human life span. Although surgical resection and adjuvant therapy can cure well-confined primary tumors, most patients will experience local recurrence or distant metastasis after surgery due to unclear tumor borders and postoperative immunosuppressive tumor microenvironment. There is largely no cure. Therefore, the use of immunotherapy to relieve the microenvironment of tumor immunosuppression is the key to inhibiting tumor recurrence after surgery. Polypeptide drugs for immunotherapy have been widely studied due ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61K47/65A61K38/16A61P35/00A61P35/04B82Y5/00B82Y40/00C07K19/00C07K1/04C07K1/02
Inventor 祁迎秋孟小草孙小凡聂广军
Owner ZHENGZHOU UNIV
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