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Tumor targeting drug and preparation method thereof

A tumor-targeting and anti-tumor drug technology, applied in the field of tumor-targeting drugs and their preparation, can solve the problems of complex preparation process, poor biocompatibility of polymer nanocarriers, and influence on normal cells, so as to avoid immune response, improve The effect of tumor treatment, the effect of improving bioavailability

Inactive Publication Date: 2019-03-29
河南省生物工程技术研究中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Targeted drugs are currently a hot spot in the research of anti-tumor drugs. Most of the common small-molecule targeted drugs are obtained by chemically modifying small-molecule drugs and protein nanocarriers or polymer nanocarriers. The preparation process is complicated, and polymer nanocarriers Poor biocompatibility, may affect normal cells in the body

Method used

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  • Tumor targeting drug and preparation method thereof
  • Tumor targeting drug and preparation method thereof
  • Tumor targeting drug and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Preparation of Target Tumor Drugs

[0032] 1. Synthesize the gene sequence targeting the tumor vector by gene synthesis: obtain the gene sequence encoding the hepatitis B virus-like particle (144 amino acid gene sequence at the C-terminal), and make the gene sequence encoding the RGD polypeptide with tumor-targeting function replace the encoding hepatitis B The gene sequence of amino acids 78-82 at the C-terminal of the virus-like particle, and the gene sequence encoding the connecting peptide is inserted between the gene sequence encoding the hepatitis B virus-like particle and the gene sequence encoding the RGD polypeptide, at the end of the C-terminus of the encoding hepatitis B virus-like particle The gene sequence is connected to the gene sequence encoding the pH-sensitive polyhistidine polypeptide to obtain the recombinant gene sequence targeting the tumor vector; the amino acid sequence of the tumor targeting vector corresponding to one of the recombina...

Embodiment 2

[0073] Example 2: The remaining steps are the same as in Example 1. When loading the drug, take 1 mL of the target protein (~1 mg / mL) recombined in step (2) and incubate with the pre-prepared dissociation solution at 4°C for 2.5 h, the total volume of the solution is 10 mL. At this time, 5 mg of doxorubicin was added to the above dissociation solution, the pH was adjusted to the pKa of doxorubicin, and the resulting mixed solution was continued to co-cultivate for 4 hours with slight shaking. Afterwards, it was transferred to a dialysis bag with a molecular weight of 8,000-14,000 Da, first placed in recombination buffer 1 and dialyzed overnight at 4°C, and replaced with recombination buffer 2 after 12 hours. The dialysis time was 48 hours in total, during which the buffer solution was changed twice to obtain the tumor-targeted drug, which was stored at -20°C.

Embodiment 3

[0074] Example 3: The remaining steps are the same as in Example 1. When loading the drug, take 1 mL of the target protein (~1 mg / mL) reconstituted in step (2) and incubate with the pre-prepared dissociation solution at 4°C for 2.5 h , the total volume of the solution is 10 mL. At this time, 1000 mg of doxorubicin was added to the above dissociation solution, the pH was adjusted to the pKa of doxorubicin, and the resulting mixed solution was continued to co-cultivate for 2 h with slight shaking. Afterwards, it was transferred to a dialysis bag with a molecular weight of 8,000-14,000 Da, first placed in recombination buffer 1 and dialyzed overnight at 4°C, and replaced with recombination buffer 2 after 12 hours. The dialysis time was 48 hours in total, during which the buffer solution was changed twice to obtain the tumor-targeted drug, which was stored at -20°C.

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Abstract

The present invention relates to the field of targeting drug delivery and particularly relates to a tumor targeting drug and a preparation method thereof. The tumor targeting drug comprises a targeting carrier and an anti-tumor drug loaded on the carrier. The targeting carrier comprises hepatitis B virus-like particles a RGD sequence recombinant protein. The tumor targeting drug can be obtained bya genetic engineering method and operation is simple. The tumor targeting drug has good targeting, high bioavailability and small side effects.

Description

technical field [0001] The invention relates to the field of targeted drug delivery, in particular to a tumor-targeted drug and a preparation method thereof. Background technique [0002] Targeted drugs are currently a hot spot in the research of anti-tumor drugs. Most of the common small-molecule targeted drugs are obtained by chemically modifying small-molecule drugs and protein nanocarriers or polymer nanocarriers. The preparation process is complicated, and polymer nanocarriers Poor biocompatibility, may affect normal cells in the body. [0003] The hepatitis B core protein virus-like particle is an empty shell structure without viral nucleic acid. Many viral structural proteins have the ability to automatically assemble into VLPs, which are similar in shape and structure to natural virus particles, and have strong immunogenicity and biological properties. active. Since VLPs do not contain viral genetic material, they are not infectious, and some of them have been succ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/42A61K45/00A61P35/00C12N15/62C12N15/70C07K19/00
CPCA61K45/00A61K47/42A61P35/00C07K14/005C07K2319/21C07K2319/33C12N15/70C12N2730/10123
Inventor 王云龙方蕊李玉林王继创张怡青邓黎黎
Owner 河南省生物工程技术研究中心
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