DNA-polymer nano material and preparation method thereof

Abstract

The invention discloses a DNA-polymer nano material and a preparation method thereof, and the preparation method comprises the following steps: carrying out reversible addition-fragmentation chain transfer polymerization on CTA and N, N-dimethylacrylamide to obtain PDMA; reacting the single-stranded DNA of which the tail end is modified with an amino group with CTA-NHS to obtain DNA-CTA; the preparation method comprises the following steps: carrying out reversible addition-fragmentation chain transfer polymerization on DNA-CTA and N, N-dimethylacrylamide to prepare DNA-PDMA; and carrying out reversible addition-fragmentation chain transfer polymerization on DNA-PDMA, PDMA and TAm, and carrying out solvent exchange self-assembly to obtain the DNA-polymer nano material. The product provided by the invention can identify multiple hydrogen bonds in core and shell structural domains.

Description

Technical Field

[0001] The present invention relates to the technical field of DNA polymer nanoparticles, and in particular to a DNA-polymer nanomaterial capable of realizing multiple hydrogen bond recognition and a preparation method thereof. Background Art

[0002] DNA nanostructures are typically constructed from sequence-defined DNA, representing unique structures with precise nanoscale features and can be used for sensing, imaging, immunomodulation, or as delivery vehicles for small molecules and oligonucleotides. Despite their extraordinary structures and superior properties, purely synthetic DNA nanostructures also have some disadvantages, such as intrinsic instability and challenges in large-scale synthesis. In contrast, DNA-polymer hybrids can also be used as building blocks for complex DNA nanostructures, offering enhanced stability and chemical diversity.

[0003] DNA is coupled to hydrophobic polymer chains to produce amphiphilic polymers. Due to the heterogeneous backbone structure, different spacing between repeating monomers and different hydrophilicities, the multiple hydrogen bonding interactions between the hydrophobic nucleobase-containing polymers and the hydrophilic DNA chains are highly selective.

[0004] DNA-polymer nanostructures possess strong stability and chemical diversity; however, the functionality of the hydrophobic polymer in the core is often overlooked, resulting in limited performance tunability of DNA-polymer nanostructures. Summary of the Invention

[0005] The technical problem to be solved by the present invention is how to improve the function of DNA-polymer.

[0006] The present invention solves the above technical problems through the following technical means:

[0007] A method for preparing a DNA-polymer nanomaterial comprises the following steps:

[0008] S1, using 2-(n-butyl trithiocarbonate) propionic acid as a chain transfer agent and N,N-dimethylacrylamide as a monomer to carry out reversible addition-fragmentation chain transfer polymerization to obtain polymer PDMA;

[0009] S2, the single-stranded DNA with modified amino group at the end is The CTA-NHS reaction yields thiolated DNA DNA-CTA;

[0010] S3, using DNA-CTA and N,N-dimethylacrylamide as raw materials, reversible addition-fragmentation chain transfer polymerization was performed to obtain DNA-PDMA;

[0011] S4, DNA-PDMA, PDMA and structural formula TAm was used as raw material for reversible addition-fragmentation chain transfer polymerization;

[0012] S5. Self-assemble the product obtained in S4 through solvent exchange to obtain the DNA-polymer nanomaterial.

[0013] Beneficial effects: The present invention adopts reversible addition-fragmentation chain transfer polymerization reaction to prepare DNA-polymer nanomaterials. Small-volume polymerization can be adopted, and successful polymerization can be achieved at a low volume of about 20 μL, thereby realizing low-volume polymerization of DNA. Nucleic acid base-containing monomers are introduced into the DNA-polymer, realizing multiple hydrogen bond recognition of the core-shell of the DNA-polymer nanoparticle.

[0014] Preferably, 2-(n-butyl trithiocarbonate) propionic acid and N-hydroxysuccinimide are used as raw materials, and a reaction is carried out in the presence of 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide to obtain CTA-NHS; the mass ratio of 2-(n-butyl trithiocarbonate) propionic acid and N-hydroxysuccinimide is 1:0.43.

[0015] Preferably, 3-benzoylthymidine is mixed with a solvent, NaH is added and stirred until no gas is generated, N-(3-bromopropyl)acrylamide is added in an ice bath, stirred for reaction and purified, and then dissolved in a mixture of trifluoroacetic acid and dichloromethane, stirred at room temperature, and purified after the reaction is completed to obtain TAm; the solvent is N,N-dimethylformamide; the mass ratio of the 3-benzoylthymidine and N-(3-bromopropyl)acrylamide is 1:1; the volume ratio of the trifluoroacetic acid and dichloromethane is 3:1; the amount ratio of the purified product after stirring the reaction and the mixture of trifluoroacetic acid and water is 2.0 g:20 mL.

[0016] Preferably, in the process of preparing PDMA, the amount ratio of 2-(n-butyl trithiocarbonate) propionic acid and N,N-dimethylacrylamide is 28.8 mg:500 μL; the solvent used is a mixture of DMF and H2O; the initiator used is 2,2'-azabis(2-imidazoline) dihydrochloride; the polymerization temperature is 70°C and the time is 2 hours.

[0017] Preferably, in S2, the DNA sequence of the single-stranded DNA with a terminal amino group modified is (CH2)6NH2-5'-TTT TTCATT ATC ACT GCT TAT TGT-3'.

[0018] Preferably, in S2, the mass ratio of the single-stranded DNA with terminal amino group modification to CTA-NHS is 1:3.24.

[0019] Preferably, the solvent used in the synthesis of thiolated DNA is DMF:H2O at a volume ratio of 1:1.

[0020] Preferably, in S2, the polymerization initiator used is 2,2'-azabis(2-imidazoline) dihydrochloride.

[0021] Beneficial effects: Using DMF:H2O in a volume ratio of 1:1 as solvent reduces the hydrolysis rate of the thiol monomer, allowing it to better bind to the amino-modified DNA.

[0022] Preferably, in S3, the usage ratio of the DNA-CTA and N,N-dimethylacrylamide is 0.43 mg:0.37 μL.

[0023] Preferably, in S4, the molar ratio of PDMA, DNA-PDMA and TAm is 0.5:0.5:300; and the solid content of PDMA, DNA-PDMA and TAm monomers used in the polymerization process is 20%.

[0024] Beneficial effects: This solid content can produce a polymer with a very high conversion rate and a large molecular weight; if the solid content is too low, the conversion rate is low and the molecular weight is small; if the solid content is too high, the polymerized monomer is not easy to dissolve.

[0025] Preferably, the DNA-polymer is obtained by introducing PDMA and copolymerizing TAm monomers with DNA-PDMA.

[0026] Beneficial effects: By introducing DNA-PDMA, the length of the hydrophilic segment of DNA is increased, the density of DNA chains in the hydrophilic shell of the nanoparticles is reduced, and the hydrophilic DNA chains outside the nanoparticles can interact with complementary single-stranded DNA through hydrogen bonds.

[0027] Preferably, after the reaction of S3 and S4 is completed, dialysis is further used to remove unreacted monomers and organic solvents, and the monomers and organic solvents are used after dialysis.

[0028] Preferably, S5 specifically includes the following steps: dissolving the product obtained in S4 in DMF, stirring the obtained solution at room temperature and dripping water into it, and dialyzing it with water to obtain the DNA-polymer nanomaterial.

[0029] Preferably, 2-(n-butyltrithiocarbonate)propionic acid, N-hydroxysuccinimide, 4-dimethylaminopyridine and a solvent are mixed, N,N'-dicyclohexylcarbodiimide is added under ice bath and stirred for reaction, after which the solid is removed and the obtained yellow liquid is concentrated under reduced pressure at room temperature and further purified by column chromatography to obtain CTA-NHS.

[0030] Preferably, in the preparation process of CTA-NHS, the solvent is dichloromethane; and the reaction is stirred for 2 h.

[0031] Preferably, in S1, 2-(n-butyl trithiocarbonate) propionic acid is placed in a reaction device, N,N-dimethylacrylamide and a solvent are added and heated to dissolve, 2,2'-azabis(2-imidazoline) dihydrochloride (VA-044) aqueous solution is added after cooling, nitrogen is introduced after freeze-thaw cycle degassing, and the reaction is carried out at 70°C for 2 hours to obtain the PDMA.

[0032] Preferably, S2 specifically includes the following steps: dissolving the single-stranded DNA with terminally modified amino groups in water, adding a DMF solution of CTA-NHS and a DMF solution of N,N-diisopropylethylamine and DMF, shaking the mixture at room temperature, then dialyzing the reaction mixture with water to remove unreacted CTA-NHS and DMF, and freeze-drying the dialyzed solution to remove moisture to obtain DNA-CTA.

[0033] Preferably, S3 specifically includes the following steps: adding DNA-CTA to a reaction device, adding a solution containing PBS and NaCl to dissolve it, adding N,N-dimethylacrylamide and VA-044 to mix evenly, degassing through a freeze-thaw cycle and then filling with nitrogen, reacting at 70°C for 30 minutes, dialyzing with water, and drying the dialyzed solution to obtain the DNA-PDMA.

[0034] Preferably, S4 specifically includes the following steps: taking DNA-PDMA and adding it to a reaction device, adding a solution containing PBS and NaCl to dissolve it, adding a DMF solution of TAm, PDMA and an aqueous solution of VA-044 and mixing them evenly, degassing after freeze-thaw cycle and filling with nitrogen, reacting at 70°C for 30 minutes, dialyzing with water, and drying the dialyzed solution.

[0035] The present invention also provides a DNA-polymer nanomaterial, which is prepared by adopting the preparation method of the DNA-polymer nanomaterial.

[0036] The polymer synthesized by the copolymerization method of the present invention can recognize the polymer chain containing complementary nucleobases or complementary DNA through hydrogen bonds in the internal nucleobase polymer chain and the external DNA of the nanostructure. Multiple hydrogen bonds can be recognized in both the core and shell domains, and it is expected to be used as a delivery carrier for small molecules and oligonucleotides. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 Schematic diagram of a reactor used in a polymerization reaction according to an embodiment of the present invention;

[0038] Figure 2 This is the hydrolysis kinetic image of CTA-NHS prepared in the present invention;

[0039] Figure 3 This is the NMR spectrum of the product prepared in Example 7 of the present invention;

[0040] Figure 4 Gel electrophoresis images of materials prepared for the present invention;

[0041] Figure 5 This is a gel electrophoresis image of the interaction between the DNA-polymer nanomaterial prepared by the present invention and cDNA;

[0042] Figure 6 This is a gel electrophoresis image of the interaction between DNA and cPA of the present invention;

[0043] Figure 7 TEM image of the interaction between the DNA-polymer nanomaterial prepared in the present invention and cPA;

[0044] Figure 8 This is a gel electrophoresis image of the simultaneous interaction between the DNA-polymer nanomaterial prepared in the present invention and cPA and cDNA;

[0045] Figure 9 TEM images of the DNA-polymer nanomaterial prepared in the present invention interacting simultaneously with cPA and cDNA. DETAILED DESCRIPTION

[0046] To make the objectives, technical solutions, and advantages of the embodiments of the present invention more clear, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0047] Unless otherwise specified, the test materials and reagents used in the following examples can be obtained from commercial sources.

[0048] If no specific techniques or conditions are specified in the examples, they can be carried out according to the techniques or conditions described in the literature in the field or according to the product instructions.

[0049] Example 1

[0050] Weigh 1.0g of 2-(n-butyl trithiocarbonate) propionic acid (CTA), 0.43g of N-hydroxysuccinimide (NHS) and 25.6mg of 4-dimethylaminopyridine (DMAP) into a flask, add 20mL of dichloromethane and stir to dissolve, then add 0.81g of N, N'-dicyclohexylcarbodiimide (DCC) under ice bath, and stir the mixture in ice bath for another 2 hours. After the reaction is completed, the solid is filtered off and the yellow liquid is concentrated under reduced pressure at room temperature. The crude product is further purified by column chromatography to obtain 2-(n-butyl trithiocarbonate) propionic acid-2,5-dioxopyrrolidine-1-ester (CTA-NHS), whose structural formula is

[0051] Example 2

[0052] Weigh 3.0g of thymine, add 30mL of acetonitrile and 12mL of pyridine, stir and dissolve, then add 11.24mL of benzoyl chloride dropwise, and stir the reactants at room temperature for 12h. Then, remove the solvent by rotary evaporation, add water and dichloromethane, extract the aqueous layer 3 times with dichloromethane, collect the organic layer, dry it with anhydrous NaSO4, and remove the solvent under vacuum. The residue is dissolved in a mixture of 30mL of dioxane, 4.1g of potassium carbonate and 30mL of water, stirred at room temperature for 2h, and recrystallized to obtain 3-benzoylthymine, whose structural formula is

[0053] Dissolve 2.3 g of 3-benzoylthymidine in 50 mL of N,N-dimethylformamide. Add 0.42 g of 60% sodium hydroxide to the solution and stir for 1 hour until gas evolution subsides. Add 2.3 g of freshly synthesized N-(3-bromopropyl)acrylamide dropwise in an ice bath and stir for 12 hours. The resulting mixture is further purified by column chromatography using EtOAc as the eluent to obtain N-(3-(3-benzoyl-1-thymidyl)propyl)acrylamide. Dissolve 2.0 g of N-(3-(3-benzoyl-1-thymidyl)propyl)acrylamide in 20 mL of a mixture of trifluoroacetic acid and dichloromethane (volume ratio = 3:1). Stir the reaction mixture at room temperature for 12 hours. After completion, remove the solvent under vacuum. N-(3-(thymidine-1-yl)propyl)-2-acrylamide (TAm) was obtained by column chromatography purification, and its structural formula is

[0054] Example 3

[0055] Weigh 28.8 mg of 2-(n-butyl trithiocarbonate) propionic acid and place it in a 10 mL ampoule. Then use a pipette to take 500 μL of N, N-dimethylacrylamide and add it to the 10 mL ampoule. Add 100 μL of DMF and 226 μL of H2O and heat to dissolve. After cooling to room temperature, add 174 μL of a 20 mg / mL aqueous solution of 2,2'-azabis(2-imidazoline) dihydrochloride (VA-044). The mixture is thoroughly degassed by three freeze-pump-thaw cycles, filled with nitrogen, and reacted in an oil bath at 70°C for 2 hours to obtain PDMA. 40 The polymer solution was diluted with 6 ml of DMF and water in a volume ratio of 1:1 and used directly in the next polymerization reaction.

[0056] Example 4

[0057] Take 100mg PDMA 40 117 mg of N-(3-(6-amino-9H-purin-9-yl)propyl)acrylamide (AAm) was added to an ampoule, 434 μL of DMF and 331 μL of H₂O were added, and the mixture was dissolved by heating. After cooling to room temperature, 103 μL of a 10 mg / mL aqueous solution of VA-044 was added. The mixture was thoroughly degassed through four freeze-thaw cycles, filled with nitrogen, and then reacted in a 70°C oil bath for 12 h. The reaction solution was precipitated in ice CH₃OH three times, and the light yellow polymer was dried in a vacuum oven at room temperature for 12 h to obtain PDMA. 40 -b-PAAm 20 Polymer, directly add pure water to dissolve the polymer to obtain PDMA 40 -b-PAAm 20 Assembled nanoparticles (cPA).

[0058] Example 5

[0059] Dissolve 1.00 mg of DNA-NH2 (DNA sequence (CH2)6NH2-5'-TTTTTC ATT ATC ACT GCT TAT TGT-3', purchased from Shanghai Sangon Biotechnology Co., Ltd.) in 344 μL of deionized water in a centrifuge tube. Add 20 mg / mL CTA-NHS dissolved in 162 μL of DMF and 60 μL of 10 μL / mL N,N-diisopropylethylamine diluted in DMF and 122 μL of DMF. Shake the mixture at room temperature for 12 hours. The reaction mixture is then dialyzed against water to remove unreacted CTA-NHS and DMF, and the dialyzed solution is freeze-dried to remove water, yielding DNA-CTA. The freeze-dried DNA-CTA is dissolved in 50 μL of a solution containing 20 mM PBS and 10 mM NaCl. The absorbance is measured using an ultramicro UV-visible spectrophotometer, and the concentration is calculated based on the absorbance at 260 nm.

[0060]

[0061] Example 6

[0062] 21.7 μL of 19.8 mg / mL DNA-CTA was added to the inner tube. After freeze-drying and dehydration, 2.1 μL of an aqueous solution containing 20 mM PBS and 10 mM NaCl was added to dissolve it. 0.37 μL of N, N-dimethylacrylamide (DMA) using neutral alumina to remove the polymerization inhibitor was added. 1 μL of a 4.82 mg / mL VA-044 aqueous solution was added and mixed evenly. The inner tube was placed in an ampoule, and 500 μL of deionized water was added to the outside of the inner tube in the ampoule. The mixture was thoroughly degassed through four freeze-thaw cycles, filled with nitrogen, and then immersed in a 70°C oil bath for 30 minutes. It was dialyzed with water to remove unreacted monomers. The dialyzed solution was freeze-dried to obtain a freeze-dried sample of DNA-PDMA. 40 .

[0063] Example 7

[0064] Take 19 μL of 17.7 mg / mL DNA-PDMA 40 The aqueous solution was added to the inner tube, and after freeze-drying to remove water, 6.9 μL of an aqueous solution containing 20 mM PBS and 10 mM NaCl was added to dissolve it. 3.5 mg of TAm was weighed and added to the inner tube, and then 7.9 μL of 13.1 mg / mL PDMA dissolved in DMF was added. 401 μL of 4.25 mg / mL VA-044 aqueous solution was added and mixed thoroughly. The inner tube was placed in an ampoule, and 500 μL of deionized water was added to the outside of the inner tube in the ampoule. The mixture was thoroughly degassed through four freeze-thaw cycles, filled with nitrogen, and then immersed in a 70°C oil bath for 30 minutes. The unreacted monomers were dialyzed with water, and the dialyzed solution was freeze-dried to obtain a lyophilized sample. The reaction conversion rate was 90% according to nuclear magnetic resonance analysis. The purified nuclear magnetic resonance image is shown below. Figure 3 As shown, it is a 1:1 molar ratio of DNA-b-PDMA 40 -b-PTAm 270 (1) and PDMA 40 -b-PTAm 270 (2); Its preparation flow chart is as follows:

[0065]

[0066] Example 8

[0067] A mixture of 1.2 mg of the lyophilized sample obtained in Example 7 was dissolved in 150 μL of DMF. The resulting solution was stirred at room temperature and heated at 10 μL min -1 1.2 mL of water was added to the solution at a rate of 1.5 mmol / l. The DNA-polymer nanomaterial capable of multiple hydrogen bond recognition was obtained by dialysis with deionized water.

[0068] Example 9

[0069] Take 108 μL of 0.93 mg mL -1 DNA-polymer nanomaterial solution was added with 7.8 μL of 10 mg mL -1 PDMA 40 -b-PAAm 20 Assembled nanoparticles (cPA), 9.2 μL 0.8 mg mL -1 cDNA-Rh (DNA with a 5'-end modified with rhodamine fluorophore and complementary to the sequence on the DNA-polymer nanomaterial, Rh-5'-ACA ATA AGC AGT GAT AAT GAAAAA-3', purchased from Shanghai Sangon Biotechnology Co., Ltd.) and 31 μL of 5xTBE buffer solution. The mixture was stirred at room temperature for 2 hours and then analyzed by TEM and PAGE, respectively.

[0070] Figure 1 This is a schematic diagram of the reactor ampoule for synthesizing DNA-polymer nanomaterials of the present invention, which can be used for small-volume synthesis.

[0071] Figure 2The hydrolysis kinetics image of 2-(n-butyl trithiocarbonate) propionic acid-2,5-dioxopyrrolidino-1-ester (CTA-NHS) in a DMF:H2O volume ratio of 1:1 (the percentage of undecomposed at each time point was calculated by NMR integration). Figure 2 It can be seen that when the volume ratio of DMF:H2O is 1:1 as solvent, CTA-NHS hydrolyzes slowly, so this condition is used when synthesizing DNA-CTA.

[0072] Figure 4 This is a gel electrophoresis image of DNA-polymer nanomaterial (M1) (gradient polyacrylamide gel electrophoresis (SDS-PAGE) image with a solid content of 4%-20%), which illustrates the successful synthesis of DNA nanomaterial. The marker in the figure is a standard DNA sample, and each band corresponds to DNA with a different number of nucleobases.

[0073] Figure 5 Gel electrophoresis images of the interaction between DNA-polymer nanomaterials and cDNA. Unstained gel electrophoresis images of the interaction between DNA-polymer nanomaterials and cDNA were obtained by annealing (the two solutions were mixed uniformly at different molar ratios, and 1 / 4 volume of 5xTBE buffer was added. The mixture was heated to 95°C in a heating block, held for 5 minutes, and then cooled to room temperature). The cDNA sequence is Rh-5'-ACA ATA AGC AGT GAT AAT GAAAAA-3' (5'-end modified with rhodamine fluorophore, purchased from Shanghai Sangon Biotechnology Co., Ltd.). From left to right, the molar ratios of cDNA:DNA polymer are 1:0; 1:1; 0.8:1; 0.5:1; 0.3:1; and 0.1:1. The bands in the upper groove become darker, while the cDNA bands in the lower groove become lighter, indicating that the DNA in the hydrophilic layer of the DNA-polymer can interact with the complementary DNA.

[0074] Figure 6 This is an unstained gel electrophoresis image of the interaction between DNA-FAM (5'-TTT TTC ATT ATC ACT GCT TAT TGT-3'-6-FAM (3' end modified with Rhodamine fluorescence, purchased from Shanghai Shenggong Bioengineering Co., Ltd.) and cPA. The fluorescently modified DNA with the same sequence as the DNA in the DNA polymer nanomaterial interacts with the polymer PDMA containing complementary nucleic acid bases. 40 -b-PAAm 20Through annealing interaction (the two solutions were mixed evenly at different molar ratios, and 1 / 4 volume of 5xTBE buffer solution was added, first raised to 95°C in a heating block, maintained for 5 minutes, and then cooled to room temperature), from left to right, the corresponding DNA-FAM:cPA molar ratios are 1:0; 1:1; 0.8:1; 0.5:1; 0.3:1; 0.1:1. There is no obvious change in the DNA-FAM band below, indicating that DNA-FAM and cPA do not interact.

[0075] Figure 7 Transmission electron microscopy (TEM) images of the interaction between DNA-polymer nanomaterials and cPA (cPA in different molar ratios was rapidly added to the DNA-polymer nanomaterial solution while stirring, and then stirred for 2 hours) (from left to right, 0 eq, 5 eq, and 10 eq of cPA were added to the DNA polymer nanoparticle solution, respectively. The scale bar in the lower right corner is 200 nm. The morphology of the nanoparticles was observed to change from a sphere to a worm, indicating that the interior of the DNA polymer nanostructure can interact with the complementary nucleobase-containing polymer to cause it to undergo a morphological transformation).

[0076] Figure 8 Figure 9 shows gel electrophoresis images of the simultaneous interaction of the DNA polymer nanomaterial (M1) with cPA and cDNA in Example 9 (left and right are gel electrophoresis images before and after staining with Gel-Red (purchased from Shanghai Shenggong Bioengineering Co., Ltd.), M1* represents the nanomaterial after interaction. Bands can be seen when M1* is unstained, indicating that the fluorescent cDNA is bound to the DNA polymer nanostructure through hydrogen bonding interactions. The stained images are used for comparison. The marker in the figure is a standard DNA sample, and each band corresponds to DNA with a different number of nucleobases.

[0077] Figure 9 This is a TEM image of the simultaneous interaction of the DNA polymer nanomaterial with cPA and cDNA in Example 9. The scale is 200 nm, indicating that the simultaneous addition of the two and the interaction with the DNA polymer nanomaterial can cause the morphology to change. Figure 8 , 9 indicates that the DNA-polymer nanomaterial can realize core-shell multiple hydrogen bond recognition.

[0078] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the various embodiments of the present invention.

Claims

1. A method for preparing a DNA-polymer nanomaterial, characterized in that: The following steps are involved: S1, using 2-(n-butyl trithiocarbonate) propionic acid as a chain transfer agent and N,N-dimethylacrylamide as a monomer to carry out reversible addition-fragmentation chain transfer polymerization to obtain polymer PDMA; S2, the single-stranded DNA with modified amino group at the end is The CTA-NHS reaction yields thiolated DNA DNA-CTA; S3, using DNA-CTA and N,N-dimethylacrylamide as raw materials, reversible addition-fragmentation chain transfer polymerization was performed to obtain DNA-PDMA; S4, DNA-PDMA, PDMA and structural formula TAm was used as raw material for reversible addition-fragmentation chain transfer polymerization; S5. Self-assemble the product obtained in S4 through solvent exchange to obtain the DNA-polymer nanomaterial.

2. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: CTA-NHS was prepared by reacting 2-(n-butyltrithiocarbonate)propionic acid and N-hydroxysuccinimide in the presence of 4-dimethylaminopyridine and N,N'-dicyclohexylcarbodiimide. The mass ratio of 2-(n-butyltrithiocarbonate)propionic acid to N-hydroxysuccinimide was 1:0.

43.

3. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: 3-Benzoylthymidine is mixed with a solvent, NaH is added and stirred until no gas is generated, N-(3-bromopropyl)acrylamide is added in an ice bath, stirred for reaction, and then purified, and then dissolved in a mixture of trifluoroacetic acid and water, stirred at room temperature, and purified after the reaction to obtain TAm; the solvent is N,N-dimethylformamide; the mass ratio of the 3-benzoylthymidine and N-(3-bromopropyl)acrylamide is 1:1; the volume ratio of the trifluoroacetic acid and dichloromethane is 3:1; and the amount ratio of the purified product after stirring reaction and the mixture of trifluoroacetic acid and dichloromethane is 2.0 g:20 mL.

4. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: In the process of preparing PDMA, the usage ratio of 2-(n-butyl trithiocarbonate) propionic acid and N,N-dimethylacrylamide is 28.8 mg:500 μL; the solvent used is a mixture of DMF and H2O; the initiator used is 2,2'-azabis(2-imidazoline) dihydrochloride; the polymerization temperature is 70°C, and the polymerization time is 2 hours.

5. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: In S2, the DNA sequence of the single-stranded DNA with a modified amino group at the terminal is (CH2)6NH2-5'-TTT TTC ATT ATC ACT GCT TAT TGT-3'.

6. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: In S2, the mass ratio of the amino-terminally modified single-stranded DNA to CTA-NHS is 1:3.

24.

7. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: In S3, the usage ratio of the DNA-CTA and N,N-dimethylacrylamide is 0.43 mg:0.37 μL.

8. The method for preparing a DNA-polymer nanomaterial according to claim 1, wherein: In S4, the molar ratio of PDMA, DNA-PDMA and TAm is 0.5:0.5:300; and the solid content of PDMA, DNA-PDMA and TAm monomers used in the polymerization process is 20%.

9. The method for preparing a DNA-polymer nanomaterial according to any one of claims 1 to 8, characterized in that: S5 specifically includes the following steps: dissolving the product obtained in S4 in DMF, stirring the obtained solution at room temperature and dripping water into it, and dialyzing it with water to obtain the DNA-polymer nanomaterial.

10. A DNA-polymer nanomaterial, characterized in that: The DNA-polymer nanomaterial is prepared by the preparation method according to any one of claims 1 to 9.

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