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Polypeptide drug conjugate and nucleic acid drug self-assembled nanoparticle and application thereof

A conjugated and self-assembly technology, applied in the field of bioengineering, can solve the problems of biological incompatibility, high toxicity, poor effect, etc., and achieve the effect of high yield, simple and efficient synthesis, and improved anti-tumor activity.

Active Publication Date: 2022-08-05
XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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Problems solved by technology

The polypeptide-drug conjugate and the polypeptide-drug conjugate-nucleic acid aptamer assembly of the present invention should solve the technical problems of cumbersome preparation and purification of nucleic acid drug carriers, high toxicity, biological incompatibility, and poor effect in the prior art

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  • Polypeptide drug conjugate and nucleic acid drug self-assembled nanoparticle and application thereof
  • Polypeptide drug conjugate and nucleic acid drug self-assembled nanoparticle and application thereof
  • Polypeptide drug conjugate and nucleic acid drug self-assembled nanoparticle and application thereof

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Embodiment Construction

[0024] The principles and features of the present invention will be described below with reference to the accompanying drawings. The examples are only used to explain the present invention, but not to limit the scope of the present invention.

[0025] 1. Design of the polypeptide-drug conjugate in the present invention

[0026] The present invention adopts a penetrating peptide composed of 9 amino acids, couples an HDAC inhibitor at the carbon end of the polypeptide, and couples a chemotherapeutic drug 5-FU at the nitrogen end, which is named as FU-NHOH. figure 1 As shown, the polypeptide sequence: 5-FU-hexyl-arginine-arginine-tryptophan-tryptophan-arginine-arginine-tryptophan-arginine-arginine- Hexanine-hydroxamic acid. Due to its positive charge, the polypeptide-drug conjugate can effectively encapsulate the nucleic acid drug AS1411 and deliver it to the nucleus.

[0027] In order to further illustrate the anti-tumor effect of the peptide-drug conjugate, we designed anothe...

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Abstract

The present invention relates to a novel polypeptide drug conjugate (PDC). The invention further provides a PDC-DNA (Polycrystalline Diamond Complex-Deoxyribose Nucleic Acid) aptamer induced self-assembly body, and the PDC-DNA aptamer induced self-assembly body is formed by self-assembly of the designed PDC and DAC aptamer AS1411. The invention also provides a method for mixing and incubating the PDC and a DNA (deoxyribonucleic acid) aptamer at normal temperature, self-assembling the PDC and the DNA aptamer into microspheres with the diameter of not more than 100nm, and enabling the nano microspheres to carry positive charges. The invention also provides a self-assembly body of the PDC-DNA aptamer, which can be used for effectively carrying a nucleic acid drug into a tumor cell nucleus. The invention also provides an application of the PDC-DNA aptamer in treatment of malignant ovarian cancer, and the purpose of tumor resistance can be achieved from multiple signal channels. The invention also provides a polypeptide-nucleic acid self-assembly body which has relatively good biocompatibility.

Description

technical field [0001] The invention belongs to the field of bioengineering, and relates to a polypeptide-drug conjugate, in particular to a polypeptide-drug conjugate-DNA aptamer-induced co-assembly and use thereof. Background technique [0002] In recent decades, nucleic acid drugs have attracted global attention due to their good efficacy in the treatment of various diseases, which are often considered to be incurable or lack effective treatments. Nucleic acid drugs are structurally unstable and do not easily penetrate cell membranes. Therefore, various strategies have been developed to encapsulate or stabilize nucleic acids so that they can be successfully transported into cells. The DNA aptamer AS1411, a G-quadruplex drug of 26 guanine-rich oligonucleotides, has been shown to interact with nucleolar proteins to inhibit the malignant proliferation of tumors in various cancer cells. AS1411 is the first nucleic acid drug in history to enter clinical trials for the treatme...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/64A61K45/06A61K31/7088A61K31/513A61K9/51A61P35/00
CPCA61K47/64A61K45/06A61K31/7088A61K31/513A61K9/5169A61P35/00A61K2300/00Y02A50/30
Inventor 王冬园张玉曾芳黄怡菲胡宽杜晶晶
Owner XIEHE HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI & TECH UNIV
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