Construction method of nano-drug carrier based on nucleic acid

A nano-drug carrier and construction method technology, applied in the field of nano-drug carrier construction, can solve the problems of lack of targeting of liposomes, single recognition function of copolymer biosafety aptamers, etc., to improve drug loading efficiency, enhance Biosafety, the effect of reducing the variation of drug resistance in cells

Active Publication Date: 2018-06-22
QINGDAO UNIV OF SCI & TECH
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] The technical problem to be solved by the present invention is to provide a new nano-medicine carrier platform by using the nucleic acid with good biocompatibility existing in large quantities in organisms as a material, and through the origami structure of DNA. The advantages of good affinity for convent

Method used

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  • Construction method of nano-drug carrier based on nucleic acid
  • Construction method of nano-drug carrier based on nucleic acid
  • Construction method of nano-drug carrier based on nucleic acid

Examples

Experimental program
Comparison scheme
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Embodiment

[0029] Example: take the case of loaded drug fluorescent paclitaxel and doxorubicin;

[0030] (1) Construction of the basic carrier structure

[0031] 1. Take 10 μL of 7 nucleic acid single-stranded (GJ1, GJ2, GJ3, GJ4, GJ5, GJ6, LOCK3) with a concentration of 10 μMol / L in a small centrifuge tube, mix them with a mixer, and place them in a 95°C water bath. Heating in medium for 4 minutes, then taking out, and slowly cooling to room temperature to obtain a basic carrier structure, which was stored at 4°C for later use.

[0032] (2) Modification of RGD cyclic polypeptide on the structural surface

[0033] 1. Take 50 μL of amino-modified nucleic acid single-stranded (MB) with a concentration of 10 μmol / L in a centrifuge tube, then add 100 μL of NHS solution with a concentration of 0.2 mol / L, react at room temperature for 30 minutes, and mix with a mixer use.

[0034] 2. Take 10 μL of surface carboxyl-modified magnetic beads into a centrifuge tube, add 100 μL of EDC solution wi...

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Abstract

The invention discloses a construction method of a nano-drug carrier based on nucleic acid. The drug carrier is of a columnar rigid structure that six groups of double helixes are mutually twisted; acolumnar going-through hole, which is 1.8-2nm in diameter, is formed in the middle of the columnar rigid structure; two ends of the carrier are blocked by locked nucleic acid single strands lock1 andlock3; one part of a blocking sequence lock3 at one end is a complementary sequence of a target aptamer mRNA; measured by dynamic light scattering, the overall length of the carrier is 40+/-4.3nm; when the target aptamer mRNA exists in cells, an entropy substitution process occurs since the number of paired bases between the target mRNA and the lock3 is much greater than a binding number between the lock3 and basic structural ports of the carrier, so that one end of the carrier is opened, and drugs in the carrier are released. According to the construction method provided by the invention, bytaking the nucleic acid existing in an organism as a raw material, a pairing situation between the bases can be regulated and controlled through artificial design, so that the nucleic acid is converted into a shape-controllable origami structure through three-dimensional folding, and the basic carrier for drug loading is obtained.

Description

technical field [0001] The invention relates to a construction method of a nucleic acid-based nano drug carrier. Background technique [0002] As an important nanomaterial, nanocarriers have broad application prospects in the field of biomedicine due to their excellent penetration and delivery properties and controlled drug release capabilities. One of the most important directions is anti-tumor targeted sustained-release drugs. development. [0003] The drug delivery system is designed to solve the problem of drug targeting. Many chemical drugs achieve good therapeutic effects in vitro, but they are not effective in the human body. The reason is that these drugs lack targeting and lack of in vivo environment. Stability requires the development of special drug delivery technologies to overcome problems such as low solubility, in vivo instability, low bioavailability and potential biological toxicity to normal tissues. A good drug delivery system is the key to solving the pr...

Claims

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Application Information

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IPC IPC(8): A61K47/64A61K47/69A61K31/704A61K47/54A61P35/00A61K31/337
CPCA61K31/337A61K31/704A61K2300/00
Inventor 吕浩源郭家义纪小婷丁彩凤
Owner QINGDAO UNIV OF SCI & TECH
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