CN-121570591-B - Mesoporous core-shell structure nano-enzyme with multienzyme activity and preparation method and application thereof

Abstract

The invention relates to the technical field of nano medical science and functional nano materials, and discloses a mesoporous core-shell structure nano enzyme with multienzyme activity, a preparation method and application thereof, wherein the nano enzyme takes gold nanorods as inner cores and iridium and oxides thereof as outer shells, and the outer shells are modified by polyethylene glycol to load photosensitizer chlorin E6, thus forming AuNR@Ir/IrO 2 -PEG/Ce6 nano enzyme which has high-efficiency Catalase (CAT) activity, the method can decompose hydrogen peroxide (H 2 O 2 ) in the tumor microenvironment and generate oxygen (O 2 ) in situ, effectively improves the treatment effect of photodynamic therapy (PDT), combines the photoacoustic imaging function through the synergistic effect of photodynamic therapy (PDT) and photothermal therapy (PTT), provides a brand-new diagnosis and treatment integrated solution for the efficient treatment and microenvironment regulation of tumors, and effectively overcomes the defects of insufficient enzyme activity and low photothermal conversion efficiency in the prior art.

Inventors

• QU JUNLE
• Gu yalong
• CHEN YU
• CHEN TIANJU
• HUANG ZHENLONG

Assignees

• 深圳大学

Dates

Publication Date

20260512

Application Date

20260127

Claims (8)

1. 1. The mesoporous core-shell structure nano enzyme with the multienzyme activity is characterized by having a core-shell structure, taking a gold nanorod as an inner core, and wrapping an outer shell formed by iridium and oxides thereof outside the inner core, wherein the outer shell has a mesoporous structure, and loading a photosensitizer chlorin E6 through the mesoporous structure; the preparation method of the mesoporous core-shell structure nano-enzyme with the multienzyme activity comprises the following steps: the preparation method of the gold nanorods comprises the steps of preparing the gold nanorods by a seed-mediated method, dispersing the gold nanorods in a dispersion medium to obtain gold nanorod dispersion liquid; The gold nanorod coating step comprises the steps of adding a hexadecyl trimethyl ammonium chloride solution into a gold nanorod dispersion liquid to obtain a mixed solution; adding an iridium trichloride solution into the mixed solution, and performing hydrothermal reaction to obtain a core-shell structure of the gold nanorod@iridium nanocluster; purifying and template removing are carried out on the core-shell structure of the gold nanorod@iridium nanocluster to obtain an iridium nanocluster coated gold nanorod nano enzyme; Adding gold nanorod nano enzyme coated by iridium nanoclusters into an amino polyethylene glycol solution to obtain a polyethylene glycol modification reaction system, reacting the polyethylene glycol modification reaction system, and collecting precipitate after the reaction is finished to obtain gold nanorod nano enzyme coated by iridium nanoclusters; Dispersing gold nanorod nano enzyme coated by a PEGylated iridium nano cluster in water to obtain a PEGylated iridium nano cluster coated gold nanorod nano enzyme solution, adding a photosensitizer chlorin E6 into the PEGylated iridium nano cluster coated gold nanorod nano enzyme solution to obtain a photosensitizer load system, reacting the photosensitizer load system under a light-proof condition, and collecting precipitate after the reaction is finished to obtain the mesoporous core-shell structure nano enzyme with multienzyme activity; The preparation method of the gold nanorods comprises the steps of taking chloroauric acid solution as a precursor, preparing seed solution under the action of a strong reducing agent and a surfactant, growing the gold nanorods by the seed solution under the action of the surfactant, a morphology regulator, a weak reducing agent and the chloroauric acid solution to obtain gold nanorod crude product solution, wherein the strong reducing agent comprises sodium borohydride solution, the surfactant comprises cetyl trimethyl ammonium bromide solution, the morphology regulator comprises silver nitrate solution, and the weak reducing agent comprises 3-aminophenol solution; The preparation method of the gold nanorods comprises the steps of centrifugally collecting a gold nanorod crude product solution, precipitating with water, dispersing the precipitate in a dispersion medium to obtain gold nanorod dispersion liquid, wherein the dispersion medium comprises deionized water.
2. 2. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the step of coating the gold nanorods, the mass ratio of the gold nanorods to cetyltrimethylammonium chloride in the mixed solution is 1:50-1:100, and the final concentration of the cetyltrimethylammonium chloride in the mixed solution is 0.04-0.08M.
3. 3. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the step of coating the gold nanorods, the mixing volume ratio of the iridium trichloride solution to the mixed solution is 1:25, and the concentration of the iridium trichloride solution is 0.05M.
4. 4. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the step of coating the gold nanorods, the hydrothermal reaction is performed after adding an iridium trichloride solution into the mixed solution, wherein after adding the iridium trichloride solution into the mixed solution, iridium ions are uniformly adsorbed on the surfaces of the gold nanorods by stirring, and then the temperature is raised to 230-250 ℃ for reaction for 1-3 hours, so that further crystallization and uniform coating of iridium nanoclusters are promoted.
5. 5. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the step of coating the gold nanorods with the iridium nanoclusters, the core-shell structures of the gold nanorods and the iridium nanoclusters are washed in ethanol to remove unreacted substances and surfactant remained on the surfaces of the core-shell structures of the gold nanorods and the iridium nanoclusters, the washed precipitate is obtained, the washed precipitate is dispersed in an ammonium nitrate ethanol solution and heated by reflux to remove the surfactant remained in the pores of the gold nanorods and the iridium nanoclusters, in the step of coating the gold nanorods with the iridium nanoclusters, the concentration of the ammonium nitrate ethanol solution is 2 g/L, and the temperature of the reflux heating is 80 ℃ and the time is 24h.
6. 6. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the polyethylene glycol modification step, the mass ratio of the iridium nanocluster coated gold nanorod nano enzyme to the amino polyethylene glycol in the polyethylene glycol modification reaction system is 1:25-1:50, and the mass concentration of the amino polyethylene glycol is 2.5 mg/mL.
7. 7. The mesoporous core-shell structured nano enzyme according to claim 1, wherein in the loading step of the photosensitizer Ce6, the mass ratio of the gold nanorod nano enzyme coated by the pegylated iridium nanocluster in a photosensitizer loading system to the photosensitizer chlorin E6 is 1:2-1:5, and the addition amount of the photosensitizer chlorin E6 in the gold nanorod nano enzyme solution coated by the pegylated iridium nanocluster is 5mg.
8. 8. Use of a mesoporous core-shell structured nanoenzyme with multienzyme activity according to any one of claims 1-7 for the preparation of a photosensitizer for inducing tumor death.

Description

Mesoporous core-shell structure nano-enzyme with multienzyme activity and preparation method and application thereof Technical Field The invention belongs to the technical field of nano-medicine and functional nano-materials, and particularly relates to a mesoporous core-shell structure nano-enzyme with multienzyme activity, and a preparation method and application thereof. Background In recent years, the development of nanomedicine has provided new strategies for the diagnosis and treatment of tumors. Modes such as photothermal therapy (PTT), photodynamic therapy (PDT) and photoacoustic imaging (PAI) have become hot spots for integrated research of tumor diagnosis and treatment. Among them, gold nanorods show great potential in terms of PTT and PAI due to their excellent photo-thermal conversion efficiency, but their therapeutic effect is deeply restricted by the penetration ability of laser light in biological tissues. The efficacy of photodynamic therapy (PDT) is limited by the tumor's intrinsic hypoxic microenvironment, a bottleneck that significantly impairs its therapeutic efficacy. The single treatment mode is difficult to meet the tumor treatment requirement, and the multi-mode combined diagnosis and treatment integration becomes a development trend. Nano-enzyme is widely used for regulating and controlling tumor microenvironment due to its activities such as Peroxidase (POD), oxidase (OXD) and Catalase (CAT). The CAT enzyme can catalyze high-concentration hydrogen peroxide (H 2O2) in tumors to decompose into oxygen, so that the anoxic state is effectively relieved, and a sufficient oxygen source is provided for photodynamic therapy. However, the conventional nano-enzyme still has the defects in the aspects of catalytic efficiency and stability, has single function, and is difficult to simultaneously meet the imaging and treatment requirements. Therefore, a new nano diagnosis and treatment technology capable of simultaneously solving the following technical problems is needed in the current tumor diagnosis and treatment field, including how to solve the limit of laser tissue penetrability on light-based diagnosis and treatment, how to improve the tumor hypoxia microenvironment efficiently so as to enhance the PDT curative effect, and how to realize the core technical problems of catalytic regulation and control, photo-thermal treatment, cooperative integration of photodynamic treatment and photoacoustic imaging functions, and the like. Disclosure of Invention The invention uses the mesoporous structure with abundant iridium nanoclusters to load the photosensitizer chlorin E6 (Ce 6), and the AuNR@Ir/IrO 2 -PEG/Ce6 nano enzyme prepared by the invention has high-efficiency CAT activity, can decompose H 2O2 in a tumor microenvironment to provide required O 2 for the enzyme, and enhances the treatment effect of PDT. And the PDT is cooperated with PTT and photoacoustic imaging to provide a brand-new integrated solution for the efficient treatment and microenvironment regulation of tumors, so that the defects in the prior art are overcome. On one hand, the invention provides a mesoporous core-shell structure nano enzyme with multienzyme activity, which has a core-shell structure, gold nanorods are used as an inner core, an outer shell formed by iridium and iridium oxide is wrapped outside the inner core, and the outer shell has a mesoporous structure and loads a photosensitizer chlorin E6 through the mesoporous structure. On the other hand, the invention provides a preparation method of the mesoporous core-shell structure nano-enzyme with the multienzyme activity, which comprises the following steps: the preparation method of the gold nanorods comprises the steps of preparing the gold nanorods by a seed-mediated method, dispersing the gold nanorods in a dispersion medium to obtain gold nanorod dispersion liquid; the gold nanorod coating step comprises the steps of adding a hexadecyl trimethyl ammonium chloride solution into a gold nanorod dispersion liquid to obtain a mixed solution; adding iridium trichloride solution into the mixed solution, and then performing hydrothermal reaction to obtain a core-shell structure of gold nanorod@iridium nanocluster, purifying and template-removing the core-shell structure of gold nanorod@iridium nanocluster to obtain iridium nanocluster coated gold nanorod nano enzyme (AuNR@Ir/IrO 2); Adding gold nanorod nano enzyme coated by iridium nanoclusters into an amino polyethylene glycol solution to obtain a polyethylene glycol modification reaction system, reacting the polyethylene glycol modification reaction system, and collecting precipitate after the reaction is finished to obtain gold nanorod nano enzyme coated by iridium nanoclusters (AuNR@Ir/IrO 2 -PEG); The method comprises the steps of loading a photosensitizer, namely dispersing gold nanorod nanoenzyme coated by PEGylated iridium nanoclusters in water to obtain a gold nanorod nanoenzyme solution coated by PEGylated