Functional nano-selenium as well as preparation method and application thereof
By preparing functionalized selenium nanoparticles (G2/PAHCit/SeNPs), the problems of insufficient stability and targeting of existing anti-tumor drugs have been solved, achieving a stronger effect in inhibiting lung cancer angiogenesis and tumor cell proliferation, thus improving the treatment efficacy of lung cancer.
Patent Information
- Application Number
- CN202511459713.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-13
- Publication Date
- 2025-12-23
AI Technical Summary
Existing anti-tumor angiogenesis drugs, such as VEGF antibodies and tyrosine kinase inhibitors, suffer from short duration of action, low hydrolysis capacity, and low stability, which hinder their application in lung cancer treatment.
A functionalized selenium nanoparticle (G2/PAHCit/SeNPs) preparation method was adopted. Through the layer-by-layer self-assembly of polyimide (G2), polyallylamine (PAH-Cit) and selenium nanoparticles (SeNPs), a nanomedicine that inhibits the proliferation of pulmonary vascular endothelial cells and lung cancer tumor cells was formed.
Functionalized selenium nanoparticles significantly improve the inhibition of angiogenesis, enhance drug targeting and delivery efficiency, reduce tissue damage, and offer more efficient potential for lung cancer treatment.
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Figure CN121177333A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of nanomedicine, in particular to a functionalized nano-selenium and a preparation method and application thereof. BACKGROUND
[0002] Lung cancer is one of the common malignant tumors. Studies have found that angiogenesis is an important factor for tumor growth, metastasis and invasion. Tumor angiogenesis can provide nutrients and oxygen for the tumor microenvironment, and promote small, dormant tumors to transform into aggressive and migratory tumors. So far, a variety of anti-angiogenic agents have been applied to clinical research as effective anti-tumor drugs, including VEGF antibody beacizumab and tyrosine kinase inhibitors sorafenib, sunitinib and pazopanib. Although these drugs are considered to be non-toxic, due to the short duration, low hydrolysis capacity and low stability of such drugs, which seriously hinder the clinical application process. Therefore, in-depth study of the mechanism of tumor angiogenesis, finding new targets and therapeutic drugs to improve the survival status of lung cancer patients is a key problem to be solved at present.
[0003] With the continuous development of nanotechnology and biotechnology, many novel properties of nanocomposites have attracted high attention. The advantages of nanocomposite drugs are that they break through the limitations of the performance of single drug components, for example, increasing the targeting of drugs and reducing toxic side effects. Many studies have shown that under the premise of not changing the molecular structure, nanomedicine can realize the amplification of drug efficiency and has a synergistic effect. Composite nanomedicine shows extraordinary effects in cancer diagnosis and treatment. SUMMARY
[0004] In order to overcome at least one of the technical problems existing in the prior art, the present application first provides a functionalized nano-selenium and a preparation method and application thereof.
[0005] The above technical problems to be solved by the present application are solved by the following technical solutions: The present application first provides a preparation method of functionalized nano-selenium (G2 / PAHCit / SeNPs), which is prepared from G2, PAH-Cit and SeNPs as raw materials.
[0006] The G2 is a polyimide.
[0007] Preferably, the PAH-Cit is prepared by the following method: (1) Dissolve polyallylamine (PAH) in NaOH solution and stir overnight to obtain a PAH solution; (2) Citraconic anhydride (Cit) was slowly added into the PAH solution and stirred overnight. During the reaction, NaOH solution was added to adjust the pH of the system to keep the pH greater than 8; (3) After the reaction, the product solution was dialyzed in weak alkaline aqueous solution for 24 h using a dialysis bag with a molecular weight cut-off of 3500; freeze-drying to obtain a white powdery product, which is PAH-Cit.
[0008] Preferably, the amount of polyallylamine (PAH) and NaOH solution in step (1) is 100 mg: 2-4 mL; Most preferably, the amount of polyallylamine (PAH) and NaOH solution in step (1) is 100 mg: 3 mL.
[0009] The NaOH solution in step (1) refers to a NaOH solution with a concentration of 0.5 M-1.5 M; Most preferably, the NaOH solution in step (1) refers to a 1.0 M NaOH solution.
[0010] Preferably, the amount of citraconic anhydride (Cit) in step (2) is 300-500 μL; Most preferably, the amount of citraconic anhydride (Cit) in step (2) is 400 μL.
[0011] Preferably, the NaOH solution in step (2) refers to a NaOH solution with a concentration of 5-8 M; Most preferably, the NaOH solution in step (2) refers to a 6 M NaOH solution.
[0012] Preferably, the SeNPs are prepared by the following method: (1) The Na2SeO3 stock solution is heated to 35-45°C, and a fresh cysteine solution is added dropwise, Then add Milli-Q water to the mixed solution to a volume of 5-15 mL; (2) Then the mixed solution is centrifuged in a centrifuge; the supernatant is removed, and the solid is resuspended in a HEPES solution to obtain nano-selenium SeNPs.
[0013] Preferably, the volume ratio of Na2SeO3 and cysteine solution in step (1) is 0.2 mL: 4-5 mL; Most preferably, the volume ratio of Na2SeO3 and cysteine solution in step (1) is 0.2 mL: 4.8 mL.
[0014] The cysteine solution in step (1) refers to a NaOH cysteine solution with a concentration of 20-30 M; Most preferably, the cysteine solution in step (1) refers to a cysteine solution with a concentration of 25 M.
[0015] Preferably, the HEPES solution in step (2) has a concentration of 5-12 M HEPES solution. Most preferably, the HEPES solution in step (3) has a concentration of 10 M HEPES solution.
[0016] The application also provides a functionalized nano selenium (G2 / PAHCit / SeNPs) prepared by the above preparation method.
[0017] The application provides an application of the above functionalized nano selenium (G2 / PAHCit / SeNPs) in preparation of an anti-lung cancer drug.
[0018] The application also provides an application of the above functionalized nano selenium (G2 / PAHCit / SeNPs) in preparation of a drug with an inhibiting effect on lung vascular endothelial cell proliferation.
[0019] The application also provides an application of the above functionalized nano selenium (G2 / PAHCit / SeNPs) in preparation of a drug carrier.
[0020] Preferably, the drug is an anti-lung cancer drug or a drug with an inhibiting effect on lung vascular endothelial cell proliferation.
[0021] Beneficial effects: The application provides a functionalized nano selenium (G2 / PAHCit / SeNPs) prepared by a novel method, and research shows that the functionalized nano selenium has a stronger inhibiting effect on angiogenesis than a commercial drug suramin. In addition, the functionalized nano selenium can not only effectively deliver functionalized nanoparticles to a target, maximize the delivery efficiency of a drug and cause less tissue damage, but also can realize high-efficiency lung cancer treatment by virtue of the superior bioactivity of nano materials. In particular, the functionalized nano selenium G2 / PAHCit / SeNPs has potential application values in inhibiting lung vascular endothelial cell proliferation and inhibiting lung cancer tumor cell proliferation, and opens up a design idea of nano drugs. BRIEF DESCRIPTION OF DRAWINGS
[0022] Figure 1 is the inhibiting effect of functionalized nano selenium on tumor angiogenesis in vivo and in vitro. (A and B) Rat group arterial ring experiment; (C and D) Mouse matrix gel experiment. DETAILED DESCRIPTION
[0023] The present application is further explained with reference to the following specific examples, which are not intended to limit the application in any way.
[0024] Example 1 Preparation of PAH-Cit Dissolve 100 mg of polyallylamine (PAH) in 3.0 mL of 1.0 M NaOH solution and stir overnight. Slowly add 400 μL of citraconic anhydride (Cit) to the PAH solution and stir overnight. During the reaction, add 6.0 M NaOH to adjust the pH of the system and maintain the pH greater than 8. After the reaction is complete, dialyze the product solution in a weakly basic aqueous solution using a dialysis bag with a molecular weight cut-off of 3500 for 24 h. Freeze-dry to obtain the product in the form of a white powder, which is PAH-Cit.
[0025] Example 2 Preparation of SeNPs Heat 0.2 mL of Na2SeO3 stock solution to 40°C, add 4.8 mL of fresh cysteine solution (25 mM) dropwise, and then add Milli-Q water to bring the volume of the mixed solution to 10 mL. Centrifuge the mixed solution twice at 15,200 g for 20 min to achieve purification. Remove the supernatant and resuspend the solid in 10 mM HEPES solution (pH = 7.4). Obtain SeNPs.
[0026] Example 3 Preparation of functionalized SeNPs Polyimide (G2), PAH-Cit and SeNPs are self-assembled by covalent bonds and electrostatic interactions to prepare functionalized SeNPs (G2 / PAHCit / SeNPs); the specific method is as follows: Dissolve 5 mg of SeNPs in 5 mL of aqueous solution by ultrasonic dissolution; after adding 10 mL of PAH-Cit (2 mg / mL) and stirring for 30 min, add 10 mL of G2 (2 mg / mL) and stir for 30 min; then centrifuge the obtained mixed solution twice at 5,000 rpm for 20 min to achieve purification; remove the supernatant and resuspend the solid in 10 mM HEPES solution (pH = 7.4); obtain functionalized SeNPs (G2 / PAHCit / SeNPs).
[0027] Example 1 In vitro inhibition of lung tumor angiogenesis by functionalized SeNPs G2 / PAHCit / SeNPs We use MTT experiment to confirm that functionalized nano selenium G2 / PAHCit / SeNPs, functionalized nano selenium G2 / PAH-Cit / SeNPs@siRNA can inhibit the proliferation of A549 lung cancer tumor cells and vascular endothelial cells. Rat aortic ring angiogenesis experiment ( Figure 1 A&B) further confirmed that the functionalized nano selenium G2 / PAHCit / SeNPs of the application has stronger effect of inhibiting angiogenesis than the commercial drug suramin. At the same time, the mouse in vivo matrigel experiment ( Figure 1 C&D) also concluded that the functionalized nano selenium G2 / PAHCit / SeNPs of the application can more obviously inhibit angiogenesis.
[0028] The above examples are the preferred embodiments of the application, but the embodiments of the application are not limited by the above examples, and any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the application shall be equivalent replacement methods and shall be included in the protection scope of the application.
Claims
1. A method for preparing functionalized selenium nanoparticles, characterized in that, It was prepared using G2, PAH-Cit and SeNPs as raw materials.
2. The method for preparing functionalized selenium nanoparticles according to claim 1, characterized in that, The PAH-Cit was prepared by the following method: (1) Dissolve polyallylamine (PAH) in NaOH solution and stir overnight to obtain PAH solution; (2) Slowly add citrate anhydride (Cit) dropwise to the PAH solution and stir overnight. During the reaction, add NaOH solution to adjust the pH of the system and maintain the pH above 8; (3) After the reaction is complete, the product solution is dialyzed in a weakly alkaline aqueous solution for 24 h using a dialysis bag with a molecular weight cutoff of 3500; freeze-drying is performed to obtain a white powder product, which is PAH-Cit.
3. The method for preparing functionalized selenium nanoparticles according to claim 2, characterized in that, In step (1), the ratio of polyallylamine (PAH) to NaOH solution is 100 mg: 2~4 mL.
4. The functionalized nano-selenium according to claim 1, characterized in that, The NaOH solution mentioned in step (2) refers to a NaOH solution with a concentration of 5~8 M.
5. The method for preparing functionalized selenium nanoparticles according to claim 1, characterized in that, The SeNPs were prepared by the following method: (1) Heat the Na2SeO3 stock solution to 35~45℃, and add fresh cysteine solution dropwise. Then add Milli-Q water until the volume of the mixed solution is 5-15 mL; (2) Then the mixed solution was centrifuged in a centrifuge; the supernatant was removed, and the solid was resuspended in HEPES solution to obtain nano-selenium SeNPs.
6. The method for preparing functionalized selenium nanoparticles according to claim 5, characterized in that, In step (1), the volume ratio of Na2SeO3 to cysteine solution is 0.2 mL: 4~5 mL.
7. Functionalized selenium nanoparticles prepared by the preparation method according to any one of claims 1 to 6.
8. The use of the functionalized selenium nanoparticles according to any one of claims 1 to 6 in the preparation of anti-lung cancer drugs.
9. The use of the functionalized selenium nanoparticles according to any one of claims 1 to 6 in the preparation of a drug having the effect of inhibiting the proliferation of pulmonary vascular endothelial cells.
10. The use of the functionalized selenium nanoparticles according to any one of claims 1 to 6 in the preparation of drug carriers.