Method for covalently linking DNA nanostructure to hydrophobic drug molecule and resultant complex
A hydrophobic drug and nanostructure technology, applied in the biological field, can solve the problems of poor connection stability, inability to precisely control the number and position of hydrophobic drug molecules, achieve strong operability, improve targeted uptake efficiency, and improve water solubility Effect
Inactive Publication Date: 2019-08-27
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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[0006] In order to solve the problem that the number and position of hydrophobic drug molecules cannot be precisely controlled and the connection stability is poor when DNA nanostructures are used as drug carriers in the prior art, the present invention provides a covalently linked DNA nanostructure and hydrophobic drug molecules. Methods and compounds obtained therefrom
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[0042] Below in conjunction with the drawings, preferred embodiments of the present invention are given and described in detail.
[0043] The method for covalently linking DNA nanostructures to hydrophobic drug molecules according to the present invention firstly includes providing multiple single-stranded DNAs and hydrophobic drug molecules with functional groups, wherein at least one single-stranded DNA is a functionalized single-stranded DNA .
[0044] In this embodiment, 20 oligonucleotide sequences having a phosphodiester bond backbone were synthesized by Invitrogen, and their nucleotide sequences were shown in SECQ ID NO:1-SECQ ID NO:20, wherein, SECQ ID The 3' end of NO:4 is marked with amino group, the 5' end of SECQ ID NO:6 is marked with amino group, the 5' end of SECQ ID NO:10 is marked with amino group, the 5' end of SECQ ID NO:11 is marked with amino group, SECQ ID NO: The 3' end of 13 is marked with an amino group, and the 5' end of SECQ ID NO:20 is marked with ...
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Abstract
The invention relates to a method for covalently linking a DNA nanostructure to a hydrophobic drug molecule, comprising the steps of providing multiple strips of single-stranded DNA and the hydrophobic drug molecule with a functional group, wherein at least one strip of single-stranded DNA is functionalized single-stranded DNA; adding an aqueous solution of the single-stranded DNA and a solution of the hydrophobic drug molecule into a first buffer to react, so that the functionalized single-stranded DNA and the functional group of the hydrophobic drug molecule generate a coupled reaction to form a covalent bond, so as to obtain a covalent linkage product; adding the covalent linkage product and the remaining single-stranded DNA into a second buffer containing magnesium ions for reaction, and assembling in sequence to form a complex of the DNA nanostructure and the hydrophobic drug molecule. The invention also provides the resultant complex; the complex comprises the DNA nanostructure and the hydrophobic drug molecule which are covalently linked. According to the method disclosed by the invention, the specific position and valence state of the hydrophobic drug molecule can be precisely regulated and controlled.
Description
technical field [0001] The invention relates to the field of biotechnology, more specifically to a method for covalently linking DNA nanostructures and hydrophobic drug molecules and the compound obtained therefrom. Background technique [0002] Tumor treatment is a complex system engineering, with chemotherapy and radiotherapy as the main means. Although traditional small-molecule chemical drugs have good therapeutic effects, they have disadvantages such as poor water solubility, low bioavailability, and strong toxicity, and require large doses of administration, which bring great toxic and side effects to patients. The development of highly efficient drug delivery carriers to improve the efficacy of drug therapy has become a hotspot in biological and medical research. [0003] Commonly used drug delivery carriers mainly include polymer carriers such as liposomes and cationic dendrimers, as well as inorganic nanomaterials represented by nano-gold and ferroferric oxide. Ho...
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IPC IPC(8): A61K47/54
CPCA61K47/549
Inventor 樊春海王丽华赵彦
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI