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Anti-tumor polypeptide nano-drug as well as preparation method and application thereof

A nano-drug and anti-tumor technology, applied in the field of nano-materials, can solve the problems of molecular structure destruction and insufficient stability, and achieve the effects of uniform particle size, conducive to enrichment and improved targeting.

Active Publication Date: 2018-05-29
THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Peptide itself has good biocompatibility and controllable degradation performance, but its stability in vivo is not enough, and its molecular structure is easily destroyed

Method used

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  • Anti-tumor polypeptide nano-drug as well as preparation method and application thereof
  • Anti-tumor polypeptide nano-drug as well as preparation method and application thereof
  • Anti-tumor polypeptide nano-drug as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0079] In this example, the anti-tumor polypeptide nano drug was prepared by the following method:

[0080] The D-peptideantagonist ( D PPA-1) polypeptide (sequence from the amino terminal is: asparagine-tyrosine-serine-lysine-proline-threonine-aspartic acid-arginine-glutamine-tyrosine amino acid-histidine-phenylalanine) as a hydrophilic tumor immunotherapy polypeptide, according to the solid-phase synthesis method and the polypeptide purification method, the substrate for MMP-2 response, 2 glycines and 2 leucines are composed Hydrophobic peptides linked to tumor immunotherapy peptides D On PPA-1, a tripeptide formed by 3 lysines is connected to the amino terminal of the hydrophobic polypeptide, and then 4 3-(diethyl)s are connected through the amino groups on the lysines (including the terminal amino group and the side chain amino group). Amino)propylthioisocyanate functional molecule (DEAP) to obtain an amphiphilic tumor immunotherapy polypeptide coupled with an acid-respo...

Embodiment 2

[0092] The purpose of this example is to determine the morphology and particle size of self-assembled nanoparticles of anti-tumor polypeptide nano-drugs in a slightly acidic solution.

[0093] The pH value of the anti-tumor polypeptide nano drug system sample obtained in Example 1 was adjusted to 6.8, and after standing at room temperature for 2 hours, the morphology was observed with a transmission electron microscope and the particle size distribution was measured with a laser particle size analyzer. like Figure 4A and Figure 4B shown. Figure 4A It is a transmission electron microscope picture, in acidic solution, the polypeptide has a nano-spherical structure, Figure 4A The particle size distribution diagram can be drawn, the particle size distribution is 40-200nm, and the average particle size is 100nm.

[0094] In addition, when the pH value of the anti-tumor polypeptide nano-drug system sample was adjusted to 6.7, 7.0, 7.1 and 7.2, the results similar to that of a...

Embodiment 3

[0097] The purpose of this example is to determine the responsiveness of anti-tumor polypeptide nano-medicines to the acidic environment of tumors in vivo.

[0098] Take 1 mg of the amphiphilic anti-tumor polypeptide coupled with DEAP (DEAP-amphipathic anti-tumor polypeptide) obtained in step (4) of Example 1, and 0.1 mg tetramethylrhodamine-5-isothiocyanate fluorescent The molecule and 0.1 mg of the quencher molecule were dissolved together in 10 μL of dimethyl sulfoxide, then added to 1 mL of phosphate buffer with a pH value of 7.4, and the mixture was sonicated for 2 min in an ultrasonic cleaner with a power of 100 W. After the sonication, the sample was left to stand at room temperature for 2 hours, then centrifuged at 10,000g for 5 minutes, and the supernatant was taken to obtain DEAP-anti-tumor polypeptide nano-drug self-assembled nanoparticles loaded with fluorescent molecules and quencher molecules at the same time. It is a relatively uniform and stable spherical struc...

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Abstract

The invention provides an anti-tumor polypeptide nano-drug as well as a preparation method and application thereof. The anti-tumor polypeptide nano-drug comprises amphiphilic anti-tumor polypeptides and acid responsiveness functional molecules coupled with the amphiphilic anti-tumor polypeptides; the amphiphilic anti-tumor polypeptides comprise hydrophilic anti-tumor polypeptides, enzyme responsiveness polypeptides and hydrophobic polypeptides. According to the anti-tumor polypeptide nano-drug prepared by the preparation method, the bottleneck that the common polypeptide drug is short in half-life period is overcome; therefore, the anti-tumor polypeptide nano-drug is a tumor immunotherapy polypeptide nano-drug which has dual responsiveness of a weak acid environment and protease on a tumorsite and is good in responsiveness, strong in stability, high in safety, high in bioavailability and good in anti-tumor function.

Description

technical field [0001] The invention belongs to the field of nanomaterials, and relates to an anti-tumor polypeptide nanomedicine and its preparation method and application. Background technique [0002] In recent years, the strategy of tumor immunotherapy based on blocking immune checkpoints has been widely studied. Compared with traditional chemotherapy and radiotherapy, this strategy has a significant and long-lasting effect and less adverse reactions, which provides hope for a real cure for tumors. The currently clinically used immune checkpoint drugs are mainly programmed death receptor 1 (programmed death 1, PD-1), programmed death ligand 1 (programmed death-ligand 1, PD-L1) and cytotoxic T lymphocyte-associated antigen. 4 (cytotoxic T-lymphocyte antigen 4, CTLA-4) antibody. In the course of clinical use, it is found that less than 30% of patients can respond positively to immune checkpoint therapy, and most patients naturally do not respond to these drugs. How to imp...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/54A61K38/16A61K45/06A61P35/00
CPCA61K9/5123A61K38/16A61K45/06A61K2300/00
Inventor 丁艳萍聂广军程科满
Owner THE NAT CENT FOR NANOSCI & TECH NCNST OF CHINA
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