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Targeting carrier, targeted drug and application of targeted drug, targeted probe and application of targeted probe

A targeting and carrier technology, applied in the field of biomedicine, can solve the problems of high cost of chemical modification, weak binding ability, low reaction yield, etc., achieve strong target cell binding ability, improve target recognition ability, and enhance multivalent binding effect of effect

Active Publication Date: 2019-03-29
HUNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When the nucleic acid aptamer binds to the drug-loaded backbone, since the two form a high-molecular-weight complex, the binding ability of the nucleic acid aptamer will be significantly reduced, thereby affecting the binding ability.
The existing technology uses nucleic acid aptamers for targeted therapy, which has a series of defects, such as low drug loading, weak binding ability, complex organic reactions, low reaction yield, poor stability and high cost of chemical modification
These deficiencies hinder their clinical application

Method used

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  • Targeting carrier, targeted drug and application of targeted drug, targeted probe and application of targeted probe
  • Targeting carrier, targeted drug and application of targeted drug, targeted probe and application of targeted probe
  • Targeting carrier, targeted drug and application of targeted drug, targeted probe and application of targeted probe

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] A targeting vector of the present invention, see figure 1 , including double-stranded polyribonucleic acid and Zy1; Zy1 forms "nano centipede" on the double-stranded polyribonucleic acid by streptavidin connection; wherein double-stranded polyribonucleic acid is made of biotin-labeled nucleic acid monomer H1 and The biotin-labeled nucleic acid monomer H2 is primed by the priming chain and hybridized alternately to form the torso of the "nano centipede"; the two sides of the torso are connected with biotin-labeled Zy1 that specifically recognizes the target cells to form the feet of the "nano centipede". The sequence of nucleic acid monomer H1 is the DNA sequence shown in SED ID NO.1 in Table 1, the sequence of nucleic acid monomer H2 is the DNA sequence shown in SED ID NO.2 in Table 1, and the sequence of the priming strand is SED in Table 1 The DNA sequence shown in ID NO.3, and the sequence of Zy1 is the DNA sequence shown in SED ID NO.4 in Table 1.

[0044] from fi...

Embodiment 2

[0055] Investigate the anti-enzyme stability of the targeting carrier of Example 1:

[0056] At 37°C, the "nano centipede" targeting carrier of Example 1 and the double-stranded polyribonucleic acid A5 in Example 1 were reacted with 0.05 unit / μL of exonuclease III in phosphate buffer for 0, 1 , 2, 4, 8, 12, 24 hours, stop the reaction with 20 mM EDTA.

[0057] The resulting product was analyzed by agarose gel electrophoresis, and the analysis results can be found in image 3 : The targeting vector remains structurally intact after exonuclease III treatment for 2 hours (see image 3 A), while dspolyRNA A5 has been completely degraded (see image 3 B), indicating that the targeting vector has better stability against enzyme digestion.

Embodiment 3

[0059] A targeting probe, including a targeting carrier and a biological imaging agent, wherein the targeting carrier is the targeting carrier of Example 1, the biological imaging agent is FITC, and FITC is loaded on the ligand of the targeting carrier through covalent modification.

[0060] A preparation method of the targeting probe of the present embodiment:

[0061] (1) In phosphate buffer, mix 25 μM nucleomonomer H1 and 25 μM nucleomonomer H2 mixture, respectively, and 5000 nM, 2500 nM, 1250 nM, 500 nM, 250 nM priming strands at room temperature , reacted for 24 hours to obtain double-stranded polyribonucleic acid B1, B2, B3, B4, B5.

[0062] (2) 50 μM streptavidin and 50 μM Zy1 labeled with a fluorescent molecule (FITC) were added to double-stranded polyribonucleic acid B1, B2, B3, B4, and B5 to obtain targeted probes. Needles b1, b2, b3, b4, b5.

[0063] (3) Take the targeting probes b1, b2, b3, b4, and b5 in step (2) respectively, and dilute them step by step to diff...

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Abstract

The invention discloses a targeted carrier, a targeted drug and application of the targeted drug, and a targeted probe and application of the targeted probe. The targeted carrier comprises double-stranded poly-ribonucleic acid and a ligand, wherein the lignd is connected to the double-stranded poly-ribonucleic acid by a connector. A nucleic acid monomer H1 and another nucleic acid monomer H2 are triggered through initiation chains, and then are intercrossed alternately to form the double-stranded poly-ribonucleic acid, and the sequence of the nucleic acid monomer H1 is shown in SED ID NO.1, and the sequence of the nucleic acid monomer H2 is shown in SED ID NO.2; the targeted drug comprises the targeted carrier and pharmic molecules, and can be used for preparing tumor targeted drugs; the targeted probe comprises the targeted carrier and biological imaging agent, and can be used for preparing a detection kit for tumor imaging and cancer cell targeted detection. The targeted carrier has the advantages of being high in drug loading efficiency, having significantly enhanced targeting ability and cellular internalization effect, and being good in biocompatibility, biodegradability and stability.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a targeting carrier, a targeting drug and the application of the targeting drug, a targeting probe and the application of the targeting probe. Background technique [0002] Cancer has become one of the most dreadful diseases of human beings due to its characteristics such as easy transfer, transformation and unlimited proliferation. Statistics show that in 2012, there were 14 million new cancer patients and 8.2 million deaths. It is estimated that by 2025, the number of new cancer patients will reach 19 million. Effectively improving diagnostic techniques and treatment methods has become an urgent need to reduce cancer incidence and mortality. Improving the diagnosis of cancer, being able to detect early cancer patients and treat them very early, thereby reducing the pain, mental and economic burden of patients, and enabling cancer patients to recover early, developing a tec...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/22A61K47/26A61K47/42A61K47/54A61K49/00A61K31/704A61P35/00
CPCA61K31/704A61K47/22A61K47/26A61K47/42A61K49/0052A61K49/0056
Inventor 羊小海李文山何磊良王青王柯敏黄晋刘剑波吴斌徐聪聪
Owner HUNAN UNIV
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