CN110669230A - Multifunctional nucleic acid-based hybrid nanogel and preparation method thereof - Google Patents
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Abstract
The invention discloses a multifunctional nucleic acid-based hybrid nanogel and a preparation method thereof, and the preparation method comprises the following steps: (1) preparing a multi-branched nucleic acid nanostructure containing sticky ends; (2) equivalently mixing the multi-branched nucleic acid nano-structures with complementary sequence adhesive tail ends obtained in the step (1) to prepare a dendritic nucleic acid network nano-structure; (3) and (3) mixing the dendritic nucleic acid network nano structure obtained in the step (2) with micromolecules or high molecular compounds of polyphenol hydroxyl to prepare the multifunctional nucleic acid-based hybrid nano gel. The nucleic acid-based hybrid nanogel disclosed by the invention is simple in preparation process, the method is green and environment-friendly, the size of the nanogel can be accurately regulated and controlled by changing the ratio of the dendritic nucleic acid network nanostructure to the micromolecule or high-molecular compound of polyphenol hydroxyl, and the efficient cell uptake efficiency is realized. By fully utilizing the multifunctionality and programmability of nucleic acid nanostructures, efficient gene/chemical combination therapy is performed.
Description
Technical Field
The invention belongs to the field of nucleic acid-based nano biomedicine, and particularly relates to a multifunctional nucleic acid-based hybrid nanogel and a preparation method thereof.
Background
Since the end of the 20 th century, the vigorous development of nano-fabrication and biotechnology has made the research of nano-materials more and more important, and a series of related research fields and industrial chains have been promoted, playing more and more important roles in the fields of environment, energy, biomedicine, and the like. The characteristic size of the nano material is between 1 and 100nm, thereby endowing the nano material with some special physical and chemical characteristics different from the conventional size material, such as remarkable surface and interface effects, small size effects, quantum size effects, macroscopic quantum tunneling effects and the like. These special properties make it show many advantages in practical applications, such as large specific surface area, high reactivity, strong adsorption capacity, strong catalytic capacity, and low toxicity. With the further development of nano science, nano materials successfully occupy a significant position in the fields of energy, information, fine chemical engineering, biomedicine and the like by virtue of excellent properties of the nano materials. Among them, biomedical nanomaterials are becoming a focus of recent research, and are used as anticancer therapeutic agents, drug delivery carriers, and the like.
Currently, delivery vectors mainly include two major types, viral vectors and non-viral vectors. Viral vectors have safety issues, especially immunogenicity and mutagenic toxicity, and are generally considered to be high risk. The non-viral vector mainly comprises liposome, polymer nanoparticles, micelle, inorganic nanoparticles and the like. However, these vectors also have drawbacks such as low biocompatibility, structural instability, difficulty in degradation in vivo, etc., and are also limited by transfection efficiency and systemic toxicity changes after injection.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a multifunctional nucleic acid-based hybrid nanogel and a preparation method thereof, and solves the problems of low transfection efficiency, poor degradability, structural instability and systemic toxicity of the existing nanocarrier.
The technical scheme of the invention is summarized as follows:
a preparation method of multifunctional nucleic acid-based hybrid nanogel mainly comprises three steps, namely:
(1) mixing a plurality of single-stranded nucleic acid sequences with equal molar ratio in equal proportion, adding a cation buffer solution, performing Polymerase Chain Reaction (PCR), and preparing a multi-branched nucleic acid nanostructure containing single-stranded sticky ends by the base complementary pairing principle;
(2) equivalently mixing the multi-branched nucleic acid nano structure with the complementary nucleic acid sequence adhesive tail end obtained in the step (1), wherein the mixing temperature is 4-40 ℃, the vibration rotating speed is 0-3000 rpm, and the reaction time is 0.5 h-3 d, so as to prepare a dendritic nucleic acid network nano structure;
(3) and (3) mixing the dendritic nucleic acid network nano structure obtained in the step (2) and the micromolecule or the macromolecular compound of the polyphenol hydroxyl according to a proper proportion, standing at room temperature, and preparing the multifunctional nucleic acid-based hybrid nano gel.
The single-stranded nucleic acid sequence has a base sequence complementary with other single strands and also has an uncompensated sticky terminal base sequence, the length ratio of the two parts of the sequence is 1: 1-5: 1, the number of the nucleic acid sequences is 2-5, and the nucleic acid sequence can be deoxyribonucleic acid (DNA) or ribonucleic acid (RNA).
The cation is Na+，Mg2+、Ca2+、Zn2+Or Fe2+Etc., preferably Mg2+(ii) a The buffer solution is any one or mixture of at least two of phosphate buffer solution, acetate buffer solution, TAE buffer solution and the like, and preferably TAE buffer solution.
The equal mixing of the multi-branched nucleic acid nanostructures means that the number of complementary cohesive ends of the multi-branched nucleic acid nanostructures is equal, ensuring that a uniform and complete dendritic nucleic acid network nanostructure is formed.
The micromolecule or high molecular compound of the polyphenol hydroxyl is a compound containing phenolic hydroxyl on benzene ring, and comprises gallic acid, pyrogallic acid, endorphin, tannic acid, epigallocatechin gallate, tea polyphenol, pyrogallol, dopamine, 3, 4, 5-trihydroxy phenylalanine or catechol or high molecular compound modified by a triphenol group. Wherein the macromolecular compound modified by catechol or triphenol group comprises polyethylene glycol, dextran, cellulose, methylcellulose, hyaluronic acid, chitosan, polylactic acid, polyvinyl alcohol or polyvinylpyrrolidone.
The dendritic nucleic acid network nano structure and the micromolecules or high molecular compounds of the polyphenol hydroxyl are mixed according to a proper proportion, specifically, the concentration of the dendritic nucleic acid network nano structure solution is 0.1-50 mu M, the mass concentration of the micromolecules or high molecular compounds of the polyphenol hydroxyl is 0.1-50 w/v%, and the mixing volume ratio of the dendritic nucleic acid network nano structure solution to the polyphenol hydroxyl is (1-100): 1-100.
The multifunctional nucleic acid-based hybrid nanogel is prepared according to the method.
The invention has the beneficial effects that: the method can accurately adjust the size of the nano particles by changing different proportions of the used substances so as to form the nucleic acid-polyphenol hydroxyl compound nano material, and the prepared multifunctional nucleic acid-based hybrid nano gel can make up the limitations of other carriers, fully exerts high biocompatibility, structural designability and functional programmability, and is used for a high-efficiency gene or medicine delivery system.
The invention adopts an environment-friendly method to prepare the novel multifunctional nucleic acid-based hybrid nanogel, the preparation process is simple, the preparation method is environment-friendly, the size of the nanogel can be accurately regulated and controlled by changing the ratio of the dendritic nucleic acid network nanostructure to the micromolecule or the macromolecular compound of the polyphenol hydroxyl, and the efficient cell uptake efficiency is realized. In addition, by fully utilizing the multifunctionality and the programmability of the nucleic acid nano structure, the nanogel can simultaneously load a plurality of nucleic acid sequences with different biological effects, and meanwhile, the hydrophobicity of the nucleic acid base can load hydrophobic drugs to carry out efficient gene/chemical combination treatment, so that the nanogel has very wide application prospect in the field of nano biomedicine.
The design principle of the invention is to fully utilize the base complementary pairing and the programmability principle of nucleic acid molecules, form a novel nucleic acid nano material through the interaction of hydrogen bonds, pi-pi accumulation and the like between the nucleic acid nano material and polyphenol hydroxyl compounds or derivatives thereof, and adjust the size of nucleic acid nano particles by adjusting the concentration ratio of the polyphenol hydroxyl compounds or the derivatives thereof to the nucleic acid molecules.
Drawings
FIG. 1 is a representation of the product of example 1 at various stages of the process for the preparation of dendritic DNA network nanostructures by gel electrophoresis;
FIG. 2 is a Scanning Electron Microscope (SEM) morphology of the multifunctional DNA hybrid nanogel prepared in example 1;
FIG. 3 is a projection electron microscope (TEM) morphology image of the RNA-based hybrid nanogel prepared in example 4;
FIG. 4 is a graph of the dynamic particle size statistics (DLS) of nanogels of different sizes of DNA-RNA hybrid nanogels prepared in example 5, the size of which can be adjusted by varying the content of nucleic acid;
FIG. 5 is the drug release profile of DNA-based hybrid nanogel prepared in example 6 at different pH conditions after loading with anticancer drug Doxorubicin (DOX).
Detailed Description
The present invention will be further illustrated by the following specific examples.
The following examples are intended to enable those skilled in the art to better understand the present invention, but are not intended to limit the present invention in any way.
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) preparation of a multi-branched nucleic acid nanostructure containing single-stranded sticky ends: mixing a plurality of single-stranded nucleic acid sequences with equal molar ratio in equal proportion, adding a cation buffer solution, performing Polymerase Chain Reaction (PCR), and preparing a multi-branched nucleic acid nanostructure containing single-stranded sticky ends by the base complementary pairing principle;
(2) preparation of dendritic nucleic acid network nanostructure: equivalently mixing the multi-branched nucleic acid nano structure with the complementary nucleic acid sequence adhesive tail end obtained in the step (1), wherein the mixing temperature is 4-40 ℃, the vibration rotating speed is 0-3000 rpm, and the reaction time is 0.5 h-3 d, so as to prepare a dendritic nucleic acid network nano structure;
(3) preparation of multifunctional nucleic acid-based hybrid nanogel: and (3) mixing the dendritic nucleic acid network nano structure obtained in the step (2) and the micromolecule or the macromolecular compound of the polyphenol hydroxyl according to a proper proportion, standing at room temperature, and preparing the multifunctional nucleic acid-based hybrid nano gel.
The preparation of the multifunctional nucleic acid-based hybrid nanogel can adopt the method. The above-described method is disclosed in order to enable a person skilled in the art to practice the invention, but is not intended to limit the invention in any way.
The invention will be further described with reference to specific embodiments and the accompanying drawings.
Example 1
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 3 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Performing polymerase chain reaction on the phosphate buffer solution to prepare a three-branch DNA nano structure containing a single-chain sticky end; mixing 2 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Phosphoric acid (D) ofSalt buffer solution, and performing polymerase chain reaction to prepare the double-branched DNA nanostructure containing single-stranded sticky ends. The cohesive end of the two-branched DNA nanostructure is complementary to the cohesive end of the three-branched DNA nanostructure, and the ratio of the length of the base complementary to other single strands in each DNA sequence to the length of the cohesive end DNA sequence is 1: 1.
(2) Equivalently mixing the three-branch and two-branch DNA nano structures with the complementary DNA sequence adhesive tail ends obtained in the step (1) according to the proportion of the adhesive tail ends, wherein the mixing temperature is 4 ℃, the vibration rotating speed is 0rpm, and the reaction time is 0.5h, so as to prepare the dendritic DNA network nano structure;
(3) and (3) mixing the dendritic DNA network nano structure obtained in the step (2) with tannic acid according to a proper proportion, standing at room temperature, and preparing the multifunctional DNA-based hybrid nanogel. The concentration of the dendritic DNA network nano-structure solution is 0.1 mu M, the mass concentration of the tannic acid solution is 0.1 w/v%, and the mixing volume ratio of the two is 1: 1.
this example performs gel electrophoresis characterization of the product at various stages of the dendritic DNA network nanostructure preparation process (fig. 1). Electrophoretic band YA,YBAnd Y isCThree single chains for constructing the three-branch DNA nano-structure are respectively arranged, and the electrophoresis strip Y is the three-branch DNA nano-structure formed by the three single chains. Electrophoretic band L1And L2To construct two single strands of the double-stranded DNA nanostructure, the electrophoretic band L is the double-stranded DNA nanostructure composed of the two strands. And (3) mixing the three-branch and two-branch DNA nano structures with complementary DNA sequence adhesive tail ends in an equal amount for half an hour according to the proportion of the adhesive tail ends to prepare the dendritic DNA network nano structure corresponding to the Y-L strip, wherein the generation of the electrophoresis strip with high molecular weight can be obviously seen from the electrophoresis gel picture, and the successful synthesis of the dendritic DNA network nano structure is proved. The multifunctional DNA-based hybrid nanogel is mixed with tannic acid to prepare multifunctional DNA-based hybrid nanogel with uniform size, and the size of the nanogel can be known to be about 200nm through SEM representation (figure 2).
Example 2
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 5 DNA single-stranded nucleic acid sequences in equal molar ratio, adding Mg2+Performing polymerase chain reaction on the TAE buffer solution to prepare a five-branch DNA nano structure containing a single-chain sticky end; mixing 2 DNA single-stranded nucleic acid sequences in equal molar ratio, adding Mg2+The TAE buffer solution of (3) is subjected to polymerase chain reaction to prepare a double-branched DNA nanostructure containing a single-stranded sticky end. The cohesive ends of the two-branched DNA nanostructures are complementary to the cohesive ends of the five-branched DNA nanostructures, and the ratio of the length of the base complementary to the other single strand in each DNA sequence to the length of its own cohesive end DNA sequence is 5: 1.
(2) Equivalently mixing the five-branch and two-branch DNA nano structures with the complementary DNA sequence adhesive tail ends obtained in the step (1) according to the adhesive tail end proportion, wherein the mixing temperature is 40 ℃, the vibration rotating speed is 3000rpm, and the reaction time is 3d, so as to prepare the dendritic DNA network nano structure;
(3) and (3) mixing the dendritic DNA network nano structure obtained in the step (2) with pyrogallic acid according to a proper proportion, standing at room temperature, and preparing the multifunctional DNA-based hybrid nanogel. The concentration of the dendritic DNA network nano-structure solution is 50 MuM, the mass concentration of the tannic acid solution is 50 w/v%, and the mixing volume ratio of the two is 1: 100.
example 3
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 3 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Performing polymerase chain reaction on the TAE buffer solution to prepare a three-branch DNA nano structure containing a single-chain sticky end; mixing 2 RNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+The TAE buffer solution is used for performing polymerase chain reaction to prepare the double-branched RNA nanostructure containing the single-stranded sticky end. The cohesive ends of the two-branched RNA nanostructures are complementary to the cohesive ends of the three-branched DNA nanostructures, and the ratio of the length of the base complementary to the other single strand in each DNA or RNA sequence to the length of its own cohesive end sequence is 3: 1.
(2) Equivalently mixing the three-branch DNA nano structure and the two-branch RNA nano structure with complementary base sequence adhesive tail ends obtained in the step (1) according to the adhesive tail end proportion, wherein the mixing temperature is 25 ℃, the vibration rotating speed is 1000rpm, and the reaction time is 24h, so as to prepare the dendritic DNA-RNA network nano structure;
(3) and (3) mixing the dendritic DNA-RNA network nano structure obtained in the step (2) with epigallocatechin gallate according to a proper proportion, standing at room temperature, and preparing the multifunctional DNA-RNA-based hybrid nano gel. The concentration of the dendritic DNA-RNA network nano-structure solution is 5 mu M, the mass concentration of the tannic acid solution is 5 w/v%, and the mixing volume ratio of the two is 1: 50.
example 4
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 4 RNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Performing polymerase chain reaction on the acetate buffer solution to prepare a four-branch RNA nanostructure containing a single-chain sticky end; mixing 3 RNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+The acetate buffer solution is used for performing polymerase chain reaction to prepare the three-branch RNA nanostructure containing the single-chain sticky end. The cohesive end of the four-branched RNA nanostructure is complementary to the cohesive end of the three-branched RNA nanostructure, and the ratio of the length of the base complementary to the other single strand in each RNA sequence to the length of its own cohesive end sequence is 4: 1.
(2) Equivalently mixing the four-branch RNA nanostructure and the three-branch RNA nanostructure with complementary base sequence adhesive terminals obtained in the step (1) according to the adhesive terminal proportion, wherein the mixing temperature is 25 ℃, the vibration rotating speed is 1200rpm, and the reaction time is 3h, so as to prepare a dendritic RNA network nanostructure;
(3) and (3) mixing the dendritic RNA network nano structure obtained in the step (2) with catechol-modified chitosan according to a proper proportion, standing at room temperature, and preparing the multifunctional RNA-based hybrid nano gel. The concentration of the dendritic RNA network nano-structure solution is 1 mu M, the mass concentration of the tannic acid solution is 1 w/v%, and the mixing volume ratio of the two is 100: 1.
the embodiment example performs TEM morphology characterization on the prepared multifunctional RNA-based hybrid nanogel, and the morphology analysis of TEM shows that the prepared nanogel has uniform morphology, a spherical structure and a particle size of about 150nm, thereby proving the successful preparation of the RNA nanogel (figure 3).
Example 5
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 3 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Performing polymerase chain reaction on the phosphate buffer solution to prepare a three-branch DNA nano structure containing a single-chain sticky end; mixing 2 RNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+The phosphate buffer solution is used for performing polymerase chain reaction to prepare the double-branched RNA nanostructure containing the single-stranded sticky end. The cohesive ends of the two-branched RNA nanostructures are complementary to the cohesive ends of the three-branched DNA nanostructures, and the ratio of the length of the base complementary to the other single strand in each DNA or RNA sequence to the length of its own cohesive end DNA sequence is 3: 1.
(2) Equivalently mixing the three-branch DNA nano structure and the two-branch RNA nano structure with complementary base sequence adhesive tail ends obtained in the step (1) according to the adhesive tail end proportion, wherein the mixing temperature is 25 ℃, the vibration rotating speed is 1200rpm, and the reaction time is 8h to prepare a dendritic DNA-RNA network nano structure;
(3) and (3) mixing the dendritic DNA-RNA network nano structure obtained in the step (2) with tannic acid according to a proper proportion, standing at room temperature, and preparing the multifunctional DNA-RNA-based hybrid nanogel. The mass concentration of the tannic acid solution is 1 w/v%, the concentration of the dendritic DNA network nano-structure solution is 1, 2.5, 5 and 10 mu M respectively, and the mixing volume ratio of the tannic acid solution to the dendritic DNA network nano-structure solution is 1:1, to prepare nanogels of different particle size sizes.
The embodiment example performs particle size characterization on the prepared multifunctional DNA-RNA-based hybrid nanogel, fixes the content of tannic acid, regulates and controls the particle size of the nanogel by changing the content of the dendritic DNA-RNA network nanostructure, and finds that increasing the content of nucleic acid can increase the size of the nanogel, thereby realizing precise regulation and control of the size of the nanogel (figure 4).
Example 6
A preparation method of multifunctional nucleic acid-based hybrid nanogel comprises the following steps:
(1) mixing 3 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+Performing polymerase chain reaction on the phosphate buffer solution to prepare a three-branch DNA nano structure containing a single-chain sticky end; mixing 2 DNA single-stranded nucleic acid sequences at equal molar ratio, adding Na+The phosphate buffer solution of (2) is subjected to polymerase chain reaction to prepare a double-branched DNA nanostructure containing a single-stranded sticky end. The cohesive end of the two-branched DNA nanostructure is complementary to the cohesive end of the three-branched DNA nanostructure, and the ratio of the length of the base complementary to the other single strand in each DNA sequence to the length of its own cohesive end DNA sequence is 4: 1.
(2) Equivalently mixing the three-branch and two-branch DNA nano structures with the complementary DNA sequence adhesive tail ends obtained in the step (1) according to the adhesive tail end proportion, wherein the mixing temperature is 37 ℃, the vibration rotating speed is 1200rpm, and the reaction time is 7h, so as to prepare the dendritic DNA network nano structure;
(3) and (3) mixing the dendritic DNA network nano structure obtained in the step (2) with tannic acid according to a proper proportion, standing at room temperature, and preparing the multifunctional DNA-based hybrid nanogel. The concentration of the dendritic DNA network nano-structure solution is 1 mu M, the mass concentration of the tannic acid solution is 1 w/v%, and the mixing volume ratio of the two is 5: 1. the prepared nanogel is loaded with anticancer drug adriamycin (DOX), and release experiments are carried out under different pH conditions.
The pH responsiveness of the nanogel is verified in the example, and the experimental result shows that the rate of releasing DOX by the nanogel is obviously accelerated under the acidic condition, so that the nanogel has obvious acid responsiveness, and has a great application prospect in the aspect of drug and gene combination therapy aiming at tumors in the future, because the nanogel has the responsiveness of a tumor acidic microenvironment (fig. 5).
Experiments prove that the multifunctional nucleic acid-based hybrid nanogels prepared in the embodiments 1 to 5 can be used for medicines slowly and controllably, and show obvious acidic environment responsiveness.
Claims (10)
1. The preparation method of the multifunctional nucleic acid-based hybrid nanogel is characterized by comprising the following steps of:
(1) mixing a plurality of single-stranded nucleic acid sequences with equal molar ratio in equal proportion, adding a cation buffer solution, performing Polymerase Chain Reaction (PCR), and preparing a multi-branched nucleic acid nanostructure containing single-stranded sticky ends by the base complementary pairing principle;
(2) equivalently mixing the multi-branched nucleic acid nano structure with the complementary nucleic acid sequence single-chain sticky tail end obtained in the step (1), wherein the mixing temperature is 4-40 ℃, the vibration rotating speed is 0-3000 rpm, and the reaction time is 0.5 h-3 d, so as to prepare the dendritic nucleic acid network nano structure;
(3) and (3) mixing the dendritic nucleic acid network nano structure obtained in the step (2) with micromolecules or high molecular compounds of polyphenol hydroxyl according to a ratio, standing at room temperature, and preparing the multifunctional nucleic acid-based hybrid nanogel.
2. The method for preparing the multifunctional nucleic acid-based hybrid nanogel according to claim 1, wherein the single-stranded nucleic acid sequence in the step (1) has a base sequence complementary to other single strands and a viscous terminal base sequence which is not complementary, and the ratio of the lengths of the two parts of the base sequence to the base sequence is 1: 1-5: 1.
3. The method for preparing the multifunctional nucleic acid-based hybrid nanogel according to claim 1, wherein the number of the plurality of single-stranded nucleic acid sequences in the step (1) is 2-5.
4. The method for preparing the multifunctional nucleic acid-based hybrid nanogel according to claim 1, wherein the single-stranded nucleic acid sequence in the step (1) is deoxyribonucleic acid or ribonucleic acid.
5. The method for preparing multifunctional nucleic acid-based hybrid nanogel according to claim 1, wherein the cation in the cation buffer solution in step (1) is Na+，Mg2+、Ca2+、Zn2+Or Fe2+Any one to more than one of mixed; the buffer solution is any one or more of phosphate buffer solution, acetate buffer solution, TAE buffer solution and the like.
6. The method of claim 1, wherein the multi-functional nucleic acid-based hybrid nanogel is formed by mixing the number of complementary sticky ends of the multi-branched nucleic acid nanostructure in step (2) in equal amounts, so as to ensure the formation of a uniform and complete dendritic nucleic acid network nanostructure.
7. The method for preparing the multifunctional nucleic acid-based hybrid nanogel as claimed in claim 1, wherein the small molecule or high molecular compound containing the phenolic hydroxyl group of the polyphenol in the step (3) is a compound containing the phenolic hydroxyl group on the benzene ring, and comprises gallic acid, pyrogallic acid, endorphin, tannic acid, epigallocatechin gallate, tea polyphenol, pyrogallol, dopamine, 3, 4, 5-trihydroxy phenylalanine or catechol or a high molecular compound modified by a triphenol group.
8. The method of claim 7, wherein the catechol or triphenol group-modified polymer compound comprises polyethylene glycol, dextran, cellulose, methyl cellulose, hyaluronic acid, chitosan, polylactic acid, polyvinyl alcohol, or polyvinylpyrrolidone.
9. The method for preparing multifunctional nucleic acid-based hybrid nanogel according to claim 1, wherein the dendritic nucleic acid network nanostructure and the small molecule or polymer compound of the polyphenol hydroxyl group in the step (3) are mixed in proportion, the concentration of the solution of the dendritic nucleic acid network nanostructure is 0.1 to 50 μ M, the mass concentration of the solution of the small molecule or polymer compound of the polyphenol hydroxyl group is 0.1 to 50 w/v%, and the volume ratio of the mixture of the two is (1 to 100): (1 to 100).
10. The multifunctional nucleic acid-based hybrid nanogel prepared by the method according to any one of claims 1 to 9.
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| US20150274768A1 (en) * | 2014-04-01 | 2015-10-01 | Research & Business Foundation Sungkyunkwan University | Method of preparing base sequence of 5'-cohesive end for synthesizing branched nucleic acid nanostructure |
| CN109554331A (en) * | 2017-09-27 | 2019-04-02 | 清华大学 | L- nucleic acid hydrogel |
| CN109810265A (en) * | 2018-12-28 | 2019-05-28 | 天津大学 | A kind of the DNA- polysaccharide hybridized hydrogel and preparation method of solvent driving volume change |
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| US20150274768A1 (en) * | 2014-04-01 | 2015-10-01 | Research & Business Foundation Sungkyunkwan University | Method of preparing base sequence of 5'-cohesive end for synthesizing branched nucleic acid nanostructure |
| CN109554331A (en) * | 2017-09-27 | 2019-04-02 | 清华大学 | L- nucleic acid hydrogel |
| CN109810265A (en) * | 2018-12-28 | 2019-05-28 | 天津大学 | A kind of the DNA- polysaccharide hybridized hydrogel and preparation method of solvent driving volume change |
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