CN111440824A - Liver-targeted cationic gene vector constructed based on lactose through amino-epoxy ring-opening reaction and preparation method thereof - Google Patents
Liver-targeted cationic gene vector constructed based on lactose through amino-epoxy ring-opening reaction and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a preparation method for constructing a liver-targeted cationic gene vector based on lactose through amino-epoxy ring-opening reaction, which comprises the following steps: 1) reacting aminated lactose and triglycidyl isocyanurate in dimethyl sulfoxide under the protection of inert gas at the reaction temperature of 40-60 ℃ for 24-48 hours; 2) and (2) after the reaction in the step 1), adding ethylenediamine, heating to 50-70 ℃, reacting for 1-3 hours, and dialyzing after the reaction is finished to obtain a white flocculent polymer. The cationic gene vector with low toxicity, high efficiency and liver targeting effect is prepared by the green amino-epoxy ring-opening reaction with mild reaction conditions based on lactose, not only can effectively realize gene transfection, but also can realize targeted delivery of nucleic acid, and can mediate CRIPSR/Cas9 gene editing system to realize effective gene editing.
Description
Technical Field
The invention belongs to the field of non-viral gene vectors, and relates to a liver-targeted cationic gene vector constructed by amino-epoxy ring-opening reaction based on lactose and a preparation method thereof.
Background
The gene vector, which is a tool for introducing a foreign gene into a cell, should itself be low in toxicity and not cause an immune response; secondly, it should be able to form a complex with a stable structure with the gene, and at the same time, it should not cause the change of the gene structure; finally, it is desirable that the vector have some targeting and degradation, which allows treatment to be directed to specific cells and reduces side effects due to retention. The gene vectors widely used by people at present include two types: viral vectors (viral vector) and non-viral vectors (non-viral vector). Viral vectors include primarily retroviruses, adenoviruses, adeno-associated viruses, and herpes simplex viruses. Such viral vectors are generally capable of easily overcoming cellular barriers and immune defense mechanisms, and thus have high transfection efficiency. However, this vector lacks safety, is liable to cause carcinogenesis and autoimmune reaction (unimmune response) and viral changes in leukocytes, and in severe cases, causes organ failure and death. Meanwhile, the viral vector also causes insertion mutation, which may cause malignant transformation of host cells, and the viral vector has limited gene-carrying ability, thus being not suitable for large-scale industrial production. In response to the above drawbacks of viral vectors, more attention has been directed to non-viral vectors. The self safety performance is high, and many gene vectors with biocompatibility or biodegradability have low toxicity and very low immunotoxicity. Compared with viral vectors, the transfection efficiency of the non-viral vector is not high, and various barriers inside and outside cells are difficult to overcome sometimes, but the non-viral vector can carry more genes, can be produced industrially on a large scale, and has high commercial potential. Therefore, the development potential thereof promotes the research and development of non-viral vectors. Cationic polymers are currently the most frequently used non-viral vectors. The cationic non-viral vector can effectively complex genes through charge interaction, so that a positively charged nanoscale complex (complex) is formed, the genes can be protected from degradation by nuclease after passing through a cell membrane, and smooth expression of the genes is guaranteed.
The lactose molecule is a disaccharide, and the lactose molecule is connected with a molecule of glucose and a molecule of galactose molecule through glycosidic bonds, and can be divided into α -lactose and β -lactose according to the difference of glucose units in the lactose.
The amino-epoxy ring opening reaction is a novel step-wise polymerization process. It relies primarily on the chemical reaction of primary amine groups with epoxide groups. Secondary amine groups and hydroxyl groups will appear as the epoxy ring is opened. Secondary amine groups can complex negatively charged nucleic acids, while hydroxyl groups can provide hydrophilicity. The amino-epoxy ring-opening reaction does not depend on harsh reaction conditions, and the reaction process is mild and green.
The traditional method for constructing the targeting gene vector is to carry out post-modification on the constructed vector by means of esterification, amidation and the like, the modification strategy is relatively simple, the preparation process is relatively complex, the characterization difficulty is large, the development of a targeting nucleic acid delivery system is greatly limited, the traditional synthetic mode is simple, convenient and controllable, the general preparation method is developed for researching the targeting vector, the target cell surface is well combined with the specific target cell surface, the PEI is not shown with the specific target cell surface, the PEI is a perfect synthetic mode, the PEI is a perfect synthetic method for recognizing the target gene, the PEI is a perfect synthetic method for recognizing the target gene delivery system, the PEI is a perfect synthetic method for the target gene, the PEI is a perfect synthetic method for recognizing the target gene of the PEI, the PEI is a perfect polysaccharide-polyethylene-N (PEI) through the PEI-polyethylene-diamine, the PEI-PEI gene transfection, the PEI-PEI, the PEI is a perfect synthetic method, the PEI-PEI gene-polysaccharide-PEI gene-PEI.
In recent years, researchers have devoted to the research work of the amino-epoxy ring opening theory and application, and can proficiently utilize the polymerization means to obtain a series of polymer materials which can be used in modern biomedicine, and simultaneously promote the application of the reaction in medical biopolymers. Ethylenediamine is a colorless liquid at room temperature and has an amine odor. Are widely used as chemical agents, agricultural chemicals, medicines, solvents, dye intermediates, rubber accelerators, surfactants, and the like. The use of amino-epoxy ring opening reactions to obtain cationic gene vectors has presented a number of problems in the research process, such as: the cationic vector has higher corresponding transfection efficiency along with the increase of molecular weight, but has higher toxicity, and how to improve the transfection efficiency and ensure the targeting effect to the greatest extent under the condition of ensuring moderate toxicity becomes the key point of attention of people; different monomers have different characteristics, some monomers have higher transfection efficiency and lower effective toxicity, and the problem that how to screen out high-efficiency and high-performance monomers is also needed to be considered by people.
Disclosure of Invention
In view of the above, the invention provides a liver-targeted cationic gene vector constructed by amino-epoxy ring-opening reaction based on lactose and a preparation method thereof. The invention specifically provides the following technical scheme:
1. a preparation method for constructing a liver-targeted cationic gene vector based on lactose through amino-epoxy ring-opening reaction comprises the following steps:
1) reacting aminated lactose and triglycidyl isocyanurate in dimethyl sulfoxide under the protection of inert gas at the reaction temperature of 40-60 ℃ for 24-48 hours;
2) and (2) after the reaction in the step 1), adding ethylenediamine, heating to 50-70 ℃, reacting for 1-3 hours, and dialyzing after the reaction is finished to obtain a white flocculent polymer.
Further, the cut-off number average molecular weight of the dialysis is 1000-7500.
Further, the cut-off number average molecular weight of the dialysis was 3000-5000.
Further, the molecular weight distribution index of the white flocculent polymer is 1.8-2.0.
Further, by mass, 0.4-0.6 part of aminated lactose, 0.1-0.4 part of triglycidyl isocyanurate and 0.1-0.3 part of ethylenediamine.
Further, by weight, 0.5-0.6 part of aminated lactose and 0.2-0.3 part of triglycidyl isocyanurate
0.2-0.3 part of ethylenediamine.
Further, by mass, 0.57 part of aminated lactose, 0.22 part of triglycidyl isocyanurate and 0.21 part of ethylenediamine.
Further, the reaction temperature in the step 1) is 50-55 ℃, and the reaction time is 24-36 hours.
Further, the reaction temperature in the step 2) is 55-60 ℃, and the reaction time is 1-2 hours.
2. The liver-targeting cationic gene vector is constructed based on lactose through amino-epoxy ring-opening reaction and prepared by the preparation method.
The invention has the beneficial effects that: the cationic gene vector with low toxicity, high efficiency and liver targeting effect is prepared by a green amino-epoxy ring-opening reaction with mild reaction conditions based on lactose, not only can gene transfection be effectively realized, but also the targeted delivery of nucleic acid can be realized, and the CRIPSR/Cas9 gene editing system can be mediated to realize effective gene editing. Not only has research significance, but also has wide application prospect and potential commercial value.
Drawings
In order to make the purpose, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings:
FIG. 1 is a graph of transfection efficiency of the prepared cationic vectors in HEK293 cells.
Fig. 2 is a graph of intracellular toxicity of the prepared cationic carriers in HEK293 cells.
FIG. 3 is a diagram of the gene editing effect generated by the prepared cationic vector mediated CRISPR/Cas9 gene editing system.
Detailed Description
Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings.
Example 1
Placing 513mg β -lactose into a 50m L round-bottom flask, adding 5m L anhydrous dimethyl sulfoxide to completely dissolve the lactose, continuously exhausting gas for 15min by using nitrogen, and sealing for later use, then dissolving 500mg carbonyldiimidazole in 5m L anhydrous dimethyl sulfoxide, sucking the dissolved liquid by using an injector, slowly injecting the dissolved liquid into β -lactose solution which is prepared previously, injecting the dissolved liquid while rapidly stirring, reacting the mixed solution at normal temperature for 24h after complete injection, dissolving 4g cystamine in 3m L anhydrous dimethyl sulfoxide after reacting for 24h, slowly injecting the cystamine into the reaction solution by using the injector, reacting for 24h at normal temperature, dropwise adding the reaction solution into 100m L acetone for precipitation after the reaction is finished, repeatedly washing and centrifuging, and drying in vacuum to obtain white powdery solid aminated lactose.
Example 2
Charging 349mg of aminated lactose and 100mg of triglycidyl isocyanurate into a 50m L round-bottom flask, adding 10m L of dimethyl sulfoxide, fully dissolving, exhausting for 15min by nitrogen, reacting for 24h at 50 ℃, adding 0.2m L of ethylenediamine after the reaction is finished, heating to 60 ℃, reacting for 2h, finally adding the reaction liquid into 50m L of water, dialyzing for 24h by a dialysis bag with molecular weight cutoff of 3500, and finally freeze-drying to obtain white flocculent polymer, which is recorded as L BP2Polymer (L BP)2) Number average molecular weight (M)n) 17500 molecular weight distribution index (M)w/Mn) Is 1.85.
Example 3
Loading 438mg of aminated lactose and 150mg of triglycidyl isocyanurate into a 50m L round-bottom flask, adding 10m L of dimethyl sulfoxide, fully dissolving, exhausting gas for 15min by nitrogen, reacting for 24h at 50 ℃, adding 0.2m L of ethylenediamine after the reaction is finished, heating to 60 ℃, reacting for 2h, finally adding the reaction liquid into 50m L of water, dialyzing for 24h by a dialysis bag with molecular weight cutoff of 3500, and finally freeze-drying to obtain white flocculent polymer L BP3Polymer (L BP)3) Number average molecular weight (M)n) 19600, molecular weight distribution index (M)w/Mn) Was 1.91.
Example 4
Charging 527mg of aminated lactose and 200mg of triglycidyl isocyanurate into a 50m L round-bottom flask, adding 10m L of dimethyl sulfoxide, fully dissolving, exhausting gas for 15min by nitrogen, reacting for 24h at 50 ℃, adding 0.2m L of ethylenediamine after the reaction is finished, heating to 60 ℃, reacting for 2h, finally adding the reaction liquid into 50m L of water, dialyzing for 24h by a dialysis bag with molecular weight cutoff of 3500, and finally freeze-drying to obtain white flocculent polymer L BP4Polymer (L BP)4) Number average molecular weight (M)n) 20000, molecular weight distribution index (M)w/Mn) Is 1.83.
Example 5
HEK293 cells were cultured at 6 × 104Per well of cellThe seeds were cultured in 24-well plates for 24h, then 20 μ LL BP/pDNA complex was added to each well at a mass ratio of 10-60, the old medium was discarded after the mass of pDNA in each well was 1.0 μ g.4h, the new medium was replaced with 500 μ L per well, 20h was further performed, the old medium was discarded, each well was washed once with 500 μ L PBS, 70 μ L cell lysate was then added, the cell lysate was lysed for 2h and observed under a microscope, after no apparent cell morphology was observed, cell debris in each well was scraped off with a cell scraper, 10 μ L was taken and added to 25 μ L substrate, and chemiluminescence intensity was measured with a luminometer, the results are shown in FIG. 1.
As can be seen from FIG. 1, the transfection efficiency of the three L BP cationic polymers increased with increasing mass ratio, while the transfection efficiency of L BP slightly decreased thereafter4The transfection efficiency in both cells was significantly higher than L BP2And L BP3This is due to L BP4The cationic polymer has more secondary amine groups, and can complex pDNA more effectively, thereby promoting the transfection efficiency, and the L BP cationic polymer can realize higher gene transfection efficiency.
Example 6
The cytotoxicity of L BP/pDNA complex in HEK293 cells is characterized by adopting an MTT method, the cells are cultured in a 96-well plate at the density of 2 × 104 cells per well, after 24h of culture, L BP/pDNA prepared in advance according to the mass ratio of 10-60 is added into each well, after 4h, old culture medium is removed, MTT solution is added, the culture is continued for 4h, the 96-well plate is taken out, the MTT solution is sucked out, the PBS is used for washing for 1-2 times, 100 mu L dimethyl sulfoxide is added into each well, the shaking is carried out for 10min, and the plate is placed on a microplate reader to read the absorbance, and the result is shown in figure 2.
It can be seen from fig. 2 that L BP did not exhibit significant cytotoxicity as the mass ratio increased, whereas PEI exhibited significantly higher cytotoxicity than L BP at the same mass ratio, thus indicating that L BP cationic polymer had lower intracellular toxicity.
Example 7
In order to characterize the gene editing effect generated by the prepared cationic vector mediated CRISPR/Cas9 gene editing systemFruit, we cultured BE L7402 cells at 2 × 105Density of individual cells per well in 6-well plates, after 24h of culture, 80. mu. L L BP per well was added4the/pCas 9-surv complex. After 48h, the cells were harvested and total DNA was extracted therefrom. The sequence with the editing site was amplified by PCR instrument and cleaved with T7E1 enzyme. Gold labeled PEI was used as a negative control.
The results are shown in FIG. 3. it can be seen from FIG. 3 that L BP was treated with T7E1 enzyme, compared to the control group and gold-labeled PEI4The experimental group shows a hybrid band after electrophoresis, and the prepared cationic vector mediated CRISPR/Cas9 gene editing system is proved to generate an effective gene editing effect, so that the L BP cationic polymer can mediate the CRIPSR/Cas9 gene editing system to realize effective gene editing.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Claims (10)
1. A preparation method for constructing a liver-targeted cationic gene vector based on lactose through amino-epoxy ring-opening reaction is characterized by comprising the following steps:
1) reacting aminated lactose and triglycidyl isocyanurate in dimethyl sulfoxide under the protection of inert gas at the reaction temperature of 40-60 ℃ for 24-48 hours;
2) and (2) after the reaction in the step 1), adding ethylenediamine, heating to 50-70 ℃, reacting for 1-3 hours, and dialyzing after the reaction is finished to obtain a white flocculent polymer.
2. The preparation method for constructing the liver-targeting cationic gene vector based on lactose through amino-epoxy ring opening reaction according to claim 1, wherein the cut-off number average molecular weight of dialysis is 1000-7500.
3. The method for preparing the liver-targeting cationic gene vector by amino-epoxy ring-opening reaction based on lactose as claimed in claim 2, wherein the cut-off number average molecular weight of the dialysis is 3000-5000.
4. The preparation method of the liver-targeting cationic gene vector constructed by the amino-epoxy ring-opening reaction based on lactose as claimed in claim 1, wherein the molecular weight distribution index of the white flocculent polymer is 1.8-2.0.
5. The preparation method of the liver-targeting cationic gene vector based on lactose through amino-epoxy ring-opening reaction according to claim 1, wherein the preparation method comprises 0.4-0.6 part of aminated lactose, 0.1-0.4 part of triglycidyl isocyanurate and 0.1-0.3 part of ethylenediamine by mass.
6. The preparation method of the liver-targeting cationic gene vector based on lactose through amino-epoxy ring-opening reaction according to claim 5, wherein the preparation method comprises, by mass, 0.5-0.6 part of aminated lactose, 0.2-0.3 part of triglycidyl isocyanurate, and 0.2-0.3 part of ethylenediamine.
7. The preparation method of claim 6, wherein the aminated lactose is 0.57 parts, triglycidyl isocyanurate is 0.22 parts, and ethylenediamine is 0.21 parts by weight.
8. The preparation method for constructing the liver-targeted cationic gene vector based on lactose through amino-epoxy ring-opening reaction according to claim 1, wherein the reaction temperature in the step 1) is 50-55 ℃, and the reaction time is 24-36 hours.
9. The preparation method for constructing the liver-targeted cationic gene vector based on lactose through amino-epoxy ring-opening reaction according to claim 1, wherein the reaction temperature in the step 2) is 55-60 ℃, and the reaction time is 1-2 hours.
10. The method of any one of claims 1-9, wherein the liver-targeting cationic gene vector is constructed by amino-epoxy ring-opening reaction based on lactose.
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|---|---|---|---|---|
| CN115197157A (en) * | 2022-07-14 | 2022-10-18 | 北京市创伤骨科研究所 | Reduction response type nucleic acid delivery vector and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006115547A2 (en) * | 2005-04-20 | 2006-11-02 | Dendritic Nanotechnologies, Inc. | Dendritic polymers with enhanced amplification and interior functionality |
| CN109337080A (en) * | 2018-09-18 | 2019-02-15 | 天津医科大学 | Phenyl boric acid polymer and its preparation method and application based on amino-epoxy base ring-opening polymerisation |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006115547A2 (en) * | 2005-04-20 | 2006-11-02 | Dendritic Nanotechnologies, Inc. | Dendritic polymers with enhanced amplification and interior functionality |
| CN109337080A (en) * | 2018-09-18 | 2019-02-15 | 天津医科大学 | Phenyl boric acid polymer and its preparation method and application based on amino-epoxy base ring-opening polymerisation |
Non-Patent Citations (2)
| Title |
|---|
| CHENYA ZHUO等: "Spatiotemporal control of CRISPR/Cas9 gene editing", 《SIGNAL TRANSDUCTION AND TARGETED THERAPY》 * |
| YU QI等: "A Lactose-Derived CRISPR-Cas9 Delivery System for Efficient Genome Editing In Vivo to Treat Orthotopic Hepatocellular Carcinoma", 《ADVANCED SCIENCE》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115197157A (en) * | 2022-07-14 | 2022-10-18 | 北京市创伤骨科研究所 | Reduction response type nucleic acid delivery vector and preparation method and application thereof |
| CN115197157B (en) * | 2022-07-14 | 2023-10-24 | 北京市创伤骨科研究所 | Reduction-responsive nucleic acid delivery vector, and preparation method and application thereof |
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