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CN-121971636-A - Nanometer assembly capable of triggering and releasing NO by using red light as well as preparation method and application of nanometer assembly

CN121971636ACN 121971636 ACN121971636 ACN 121971636ACN-121971636-A

Abstract

The invention relates to the technical field of biomedical materials, in particular to a nanometer assembly capable of triggering and releasing NO by using red light, a preparation method and application thereof. The nanometer assembly is prepared from an amphiphilic block polymer with a polyethylene glycol hydrophilic end and a hydrophobic section containing NO donor molecules and photocatalyst molecules through a hydrophilic-hydrophobic self-assembly forming method, wherein the photocatalyst molecules in the amphiphilic block polymer are excited under red light irradiation, and can trigger the decomposition of the NO donor molecules through an electron transfer process, so that the time-space controllable regulation of NO release is realized. The nanometer assembly has the characteristics of red light response, excellent biological safety and antibacterial performance, and has wide application prospects in the aspects of antibacterial, anti-inflammatory and the like. In addition, the invention utilizes the characteristics of large tissue penetration depth and low phototoxicity of red light to effectively overcome the problem of limited penetration depth of the traditional ultraviolet light or blue light response NO donor molecular monomer.

Inventors

  • HE KEWU
  • Gan Guihai
  • LI WUHAO
  • SHEN ZHIQIANG

Assignees

  • 安徽医科大学附属巢湖医院

Dates

Publication Date
20260505
Application Date
20260119

Claims (10)

  1. 1. A nano-assembly for releasing NO by triggering with red light, which is characterized in that the nano-assembly is prepared from a raw material system containing amphiphilic block polymers by a hydrophilic-hydrophobic self-assembly forming method; the structural formula of the amphiphilic block polymer is one of the formula (I), the formula (II), the formula (III) and the formula (IV): ; In the formulas (I) - (IV), R 1 is selected from one of the formulas (rI), (rII) and (rIII), R 2 is selected from one of the formulas (rIV) and (rV), m is an integer between 2 and 100, n is an integer between 2 and 100, x is 0.01-0.99, y is 0.01-0.99, and x+y=1; ; In the formula (rI) to the formula (rIII), R 3 、R 4 is independently selected from one of hydrogen, nitro, methoxy, trifluoromethyl and cyano.
  2. 2. The nano-assembly for releasing NO by red light triggering according to claim 1, wherein the amphiphilic block polymer is prepared by polymerization reaction of a component system comprising NO donor molecular monomers, photocatalyst molecular monomers and macromolecular chain transfer agent PEG-CTA; Wherein, the structural formula of the macromolecular chain transfer agent PEG-CTA is as follows: wherein m is an integer between 2 and 100; the NO donor molecular monomer is one of the following structures: ; The photocatalyst molecular monomer is one of the following structures: 。
  3. 3. The nano-assembly for releasing NO triggered by red light according to claim 1, wherein the amphiphilic block polymer has a number average molecular weight of 200-35000 Da.
  4. 4. The red light triggered release NO nano-assembly of claim 1, wherein the particle size of the nano-assembly is 20-800 nm.
  5. 5. A method for preparing a nano-assembly for triggering release of NO by red light according to any one of claims 1 to 4, comprising the steps of: (1) Respectively synthesizing NO donor molecular monomers and photocatalyst molecular monomers; (2) Carrying out polymerization reaction on a component system containing the NO donor molecular monomer, the photocatalyst molecular monomer and a macromolecular chain transfer agent PEG-CTA to obtain an amphiphilic block polymer; (3) And preparing the amphiphilic block polymer into the nano assembly by a hydrophilic-hydrophobic self-assembly forming method.
  6. 6. The method of claim 5, wherein in the step (2), the ratio of the amounts of the substances of the NO donor monomer, the photocatalyst monomer and the macromolecular chain transfer agent PEG-CTA is (1-2): 10-30): 0.5-2.
  7. 7. The method for preparing a nano-assembly for releasing NO according to claim 5, wherein in the step (2), the polymerization reaction is performed at a temperature of 30 to 40 ℃ for 10 to 30 hours.
  8. 8. The method for preparing a nano-assembly for releasing NO triggered by red light according to claim 5, wherein in step (3), the amphiphilic block polymer is prepared by a hydrophilic-hydrophobic self-assembly forming method, and specifically comprises: dissolving the amphiphilic block polymer in an organic solvent to prepare an organic phase solution; And (3) self-assembling the organic phase solution by a nano flash precipitation method, and then obtaining the nano assembly through dialysis treatment.
  9. 9. The method for preparing the nano-assembly for releasing NO by red light triggering according to claim 8, wherein the organic solvent is one of tetrahydrofuran, dimethyl sulfoxide, N-dimethylformamide and 1, 4-dioxane; And/or, in the organic phase solution, the mass concentration of the amphiphilic block polymer is 0.01-10 g/L.
  10. 10. Use of the red light triggered release NO nano-assembly of any one of claims 1-4 or the nano-assembly prepared by the preparation method of any one of claims 5-9 in the preparation of an antibacterial drug.

Description

Nanometer assembly capable of triggering and releasing NO by using red light as well as preparation method and application of nanometer assembly Technical Field The invention relates to the technical field of biomedical materials, in particular to a nanometer assembly capable of triggering and releasing NO by using red light, a preparation method and application thereof. Background Nitric Oxide (NO) is an endogenous gas signaling molecule that plays important physiological and pathological regulatory roles in the body, including vasodilation, platelet aggregation inhibition, immune response regulation, and nerve conduction promotion. In addition to physiological functions, NO has antibacterial activity, and can achieve sterilization by destroying bacterial cell membranes, inhibiting respiratory chain enzyme activity, inducing DNA damage, interfering with protein synthesis, etc. Unlike traditional antibiotics, the antibacterial mechanism of NO has multiple targets and does not depend on specific receptors, so that the NO has an inhibitory effect on drug-resistant strains as well, and has unique therapeutic potential under the background of increasingly serious risk of antibiotic resistance. However, clinical conversion of NO in antimicrobial therapy presents significant challenges in that NO has a very short half-life and is very easily oxidized or diffusely cleared under physiological conditions, resulting in difficulty in maintaining effective concentrations at the affected lesions, and in that NO gas is used directly, with the risk of uncontrollable doses and systemic toxicity. For this reason, researchers have developed a variety of NO release systems (e.g., NONOates, RSNOs and metal-NO complexes) in an effort to achieve controlled release. However, these systems generally rely on ultraviolet or blue light excitation, which has the problem of limited tissue penetration depth, and the released NO is difficult to function in environments with deep bacterial infections. The red light has the characteristics of large tissue penetration depth, low phototoxicity, remote accurate control and the like, and has important application value in the biomedical field. Therefore, the development of a novel NO release system which can be excited by red light has important practical significance for expanding the clinical transformation of NO in antibacterial treatment. Disclosure of Invention The invention provides a nano assembly capable of triggering and releasing NO by red light, which has red light response characteristic, excellent biosafety and antibacterial performance. The invention also provides a preparation method of the nanometer assembly capable of triggering and releasing NO by using the red light, and the nanometer assembly with the characteristics of red light response, excellent biosafety and antibacterial performance can be prepared by using the method. The invention also provides an application of the nanometer assembly for releasing NO by triggering with the red light or the nanometer assembly prepared by the preparation method in preparation of antibacterial drugs. The nano-assembly has red light response characteristic, excellent biosafety and antibacterial property, so that the nano-assembly can be used for preparing antibacterial medicines. The first aspect of the present invention provides a nano-assembly for releasing NO triggered by red light, which is prepared from a raw material system comprising an amphiphilic block polymer by a hydrophilic-hydrophobic self-assembly forming method; the structural formula of the amphiphilic block polymer is one of the formula (I), the formula (II), the formula (III) and the formula (IV): ; In the formulas (I) - (IV), R 1 is selected from one of the formulas (rI), (rII) and (rIII), R 2 is selected from one of the formulas (rIV) and (rV), m is an integer between 2 and 100, n is an integer between 2 and 100, x is 0.01-0.99, y is 0.01-0.99, and x+y=1; ; In the formula (rI) to the formula (rIII), R 3、R4 is independently selected from one of hydrogen, nitro, methoxy, trifluoromethyl and cyano. The nanometer assembly capable of triggering and releasing NO by using the red light is prepared by polymerizing a component system comprising NO donor molecular monomers, photocatalyst molecular monomers and macromolecular chain transfer agent PEG-CTA; Wherein, the structural formula of the macromolecular chain transfer agent PEG-CTA is as follows: wherein m is an integer between 2 and 100; the NO donor molecular monomer is one of the following structures: ; The photocatalyst molecular monomer is one of the following structures: 。 according to the nano-assembly capable of triggering and releasing NO by using the red light, the number average molecular weight of the amphiphilic block polymer is 200-35000 Da. The nanometer assembly capable of triggering and releasing NO by the red light has the particle size of 20-800 nm. The second aspect of the present invention provides a