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Active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof

An active targeting and nano-carrier technology, applied in the field of biomedicine, can solve the problems of undetectable tumor sites, low encapsulation efficiency, and poor targeting of tumor cells, achieving in vivo stability and broad application prospects , the effect of high packing efficiency

Active Publication Date: 2019-09-17
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The invention solves the technical problems that nanocarriers have poor targeting to tumor cells, low encapsulation efficiency, and inability to detect tumor sites in the prior art

Method used

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  • Active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof
  • Active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof
  • Active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Preparation method of active targeting amphiphilic polypeptide nanocarrier

[0044] (i) Preparation of amphiphilic polypeptide molecules:

[0045] (1) Take 0.3 grams of Rink Amide-AM resin to the peptide synthesis device, add dry N,N-dimethylformamide to soak the resin for 2 hours to make it fully swell, and finally discharge the solvent N,N-dimethylformamide . Then use piperidine:N,N-dimethylformamide solution (10 mL) with a volume ratio of 1:4 to remove the protective group of the resin, and react twice for 20 minutes each time. Then wash the resin with 10mL N,N-dimethylformamide repeatedly for 3 times, each time for 5 minutes, take a little resin and add it to the ethanol solution of ninhydrin and phenol, heat to boiling, observe the color change of the resin, if The resin turns blue or even black, indicating that the protective group of the resin has been successfully removed, and the coupling of the first amino acid can be carried out. If the color of ...

Embodiment 8

[0057] Example 8: Preparation method of active targeting amphiphilic polypeptide nano-drug carrier loaded with anti-tumor drugs

[0058] (i) Preparation of an amphiphilic polypeptide molecule (DACP) containing two hydrophobic alkyl chains: refer to steps (1)-(9) in Example 1.

[0059] (ii) Preparation of nano-drug carrier: at room temperature, according to the mass ratio of the drug to the amphiphilic polypeptide molecule being 1: (2-10), 5 mg of the amphiphilic polypeptide molecule and the hydrophobic antineoplastic drug camptothecin were dissolved in In 170 microliters of dichloromethane solution, remove the dichloromethane solution by rotary evaporation, disperse it in water under ultrasonic conditions, sonicate for 30 minutes, filter the membrane to remove unencapsulated chemotherapeutic drugs, and obtain the product.

[0060] Morphological observation

[0061] (1) Observing the DACP nano-carrier with an electron microscope, it was found that the prepared nano-carrier was...

Embodiment 9

[0063] Embodiment 9: Determination of Encapsulation Efficiency of Nanocarriers of the Present Invention

[0064] (1) Draw the standard working curve, take by weighing 2.5mg camptothecin and dissolve it in dichloromethane, equipotentially dilute 7 concentrations, each concentration is 1mL, utilize ultraviolet spectrophotometer to measure camptothecin in dichloromethane in ultraviolet Absorbance at the absorption peak; draw a standard working curve.

[0065] (2) The aqueous solution of the nano drug carrier (DACP@CPT NPs) in Example 5 was lyophilized, then dissolved in dichloromethane, and the absorbance value of the antitumor drug in the dichloromethane solution was measured by an ultraviolet spectrophotometer;

[0066] (3) Bring the absorbance value measured in step (2) into the standard working curve, and by calculation, obtain the entrapped mass of camptothecin;

[0067] (4) Calculate the encapsulation efficiency of camptothecin by nanocarriers according to the concentratio...

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Abstract

The invention provides an active targeting type amphipathic polypeptide nano-drug carrier and preparation and application thereof, and belongs to the technical field of biological medicines. According to an amphipathic polypeptide, an alkyl chain serves as the hydrophobic end, a polypeptide chain with active targeting functional and side chain modification fluorescent functional molecules serves as the hydrophilic end, and an anti-tumor drug is wrapped in a hydrophobic cavity of a micelle formed by self-assembling the amphipathic polypeptide. The nano-carrier can actively target tumor cells and enter the tumor cells through receptor-mediated endocytosis, the amphipathic polypeptide and phospholipid molecules have strong interaction, and the phagocytosis of a nano-drug by tumor cells is promoted. In the process, tracing can be conducted through fluorescent imaging of fluorescent functional molecules modified on the polypeptide chain, and the tumor imaging aim is realized. Finally, the anti-tumor drug is slowly released to kill tumor cells and restrain the growth of tumors. The amphipathic polypeptide nano-carrier is free of toxin, high in biocompatibility and remarkable in anti-tumor efficiency, and the tumor diagnosis and treatment can be integrated.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. Specifically, the present invention provides an active targeting amphiphilic polypeptide nano drug carrier and its preparation and application. Background technique [0002] Peptide self-assembly is a very common phenomenon in living organisms and plays an important role in many life activities and biological functions. Polypeptides are formed by linking α-amino acids with peptide bonds, and have outstanding advantages such as good biocompatibility, easy chemical modification and excellent assembly properties. Among them, amphiphilic polypeptide molecules have amphiphilic properties similar to natural phospholipid molecules. The molecular structure has hydrophobic segments and hydrophilic end groups. The hydrophobic interaction between hydrophobic segments and the hydrogen between hydrophilic polypeptide segments Driven by bond coordination, polypeptide molecules can self-assemble into regu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K45/00A61K47/42A61K49/00A61P35/00
CPCA61K9/1075A61K45/00A61K47/42A61K49/0041A61K49/0056A61K49/0082A61P35/00
Inventor 朱锦涛殷小燕耿振蒋皓马腾
Owner HUAZHONG UNIV OF SCI & TECH
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