CN115531561A - Hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme - Google Patents

Hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme Download PDF

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CN115531561A
CN115531561A CN202211258437.6A CN202211258437A CN115531561A CN 115531561 A CN115531561 A CN 115531561A CN 202211258437 A CN202211258437 A CN 202211258437A CN 115531561 A CN115531561 A CN 115531561A
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hydrogen peroxide
nanoenzyme
diagnosis
targeting
treatment
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陈超毅
梁晓龙
马骋
汤清双
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Tsinghua University
Peking University Third Hospital
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Tsinghua University
Peking University Third Hospital
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Abstract

The application provides a hydrogen peroxide response dual-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme and a preparation method and application thereof, wherein the nano enzyme consists of ferroferric oxide nano particles modified by oleic acid and 3,3',5,5' -tetramethyl benzidine molecules, and the surface of the nano enzyme is modified with distearoyl phosphatidyl ethanolamine-polyethylene glycol molecules and distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD molecules. The nano enzyme generates a photo-thermal medium through hydrogen peroxide response in an organism, realizes hydrogen peroxide response type photo-acoustic signal enhancement, and simultaneously realizes photochemical kinetic treatment of tumors.

Description

Hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme
Technical Field
The invention relates to the technical field of biomedicine, in particular to a hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme and a preparation method and application thereof.
Background
Hydrogen peroxide is an endogenously produced reactive oxygen species, is highly reactive towards biological molecules, and is involved in a variety of physiological and pathological processes. Many diseases, including cancer, inflammation, cardiovascular and neurological diseases, result in elevated levels of hydrogen peroxide. Therefore, the visual detection and quantification of hydrogen peroxide is of great significance for the diagnosis of early stage tumors and other glutathione-related diseases. In addition, nanoenzyme-mediated fenton's reaction can make good use of hydrogen peroxide in the tumor microenvironment to generate hydroxyl radicals and is used for chemokinetic treatment. However, due to the limitations of hydrogen peroxide concentration in the tumor microenvironment and delivery efficiency of nanoenzymes, complete elimination of tumors is difficult to achieve with nanoenzyme-mediated chemokinetic therapy. The tumor photothermal diagnosis and treatment has wide application prospect due to high spatial and temporal resolution, tumor specificity and non-invasiveness. However, the physical limitation of light penetration and the non-specificity of traditional photothermal mediators make it difficult to achieve accurate diagnosis and complete elimination of tumors.
The photoacoustic imaging is a biological imaging technology which can be applied to clinical and preclinical researches, has optical contrast and ultrasonic penetration depth, expands structural images and functional images based on different chromophores to acoustic imaging depth, breaks through optical scattering limit, can detect spectral information of deep biological tissues, and has the advantages of non-invasion, no radiation, high imaging speed, low cost and the like. Conventional photoacoustic imaging methods achieve imaging of deep biological tissues by virtue of the contrast in light absorption (e.g., hemoglobin, melanin, fat, etc.) produced by the endogenous photoacoustic chromophores in the organism. Therefore, the photoacoustic imaging based on the binding specificity response type probe has wide application prospect in the detection of deep tissue tumor in clinic and the preclinical research.
The prior art discloses that a nanoparticle reagent based on horseradish peroxidase or metal nanoenzyme can be used for the photo-acoustic imaging and photochemical kinetic diagnosis and treatment integration of hydrogen peroxide. However, the above techniques still suffer from low delivery efficiency, incomplete treatment, and the like.
In conclusion, the development of a diagnosis and treatment integrated nanoenzyme having hydrogen peroxide response performance and higher delivery efficiency and treatment effect for in vivo hydrogen peroxide detection and photochemical kinetic treatment is a technical problem to be solved in the field.
Disclosure of Invention
In order to solve the problems, the invention provides the hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme and the preparation method and the application thereof.
On one hand, the application provides hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme, the nanoenzyme consists of oleic acid modified ferroferric oxide nanoparticles and 3,3',5,5' -tetramethylbenzidine molecules, and distearoyl phosphatidyl ethanolamine-polyethylene glycol molecules and distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD molecules are modified on the surface of the nanoenzyme.
Further, the average particle size of the nano enzyme is 16 nanometers.
In another aspect, the present application provides a method for preparing the nanoenzyme, comprising:
(1) Dissolving ferroferric oxide nano-particles modified by oleic acid, 3,3',5,5' -tetramethyl benzidine, distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD;
(2) Carrying out water bath ultrasonic treatment;
(3) Removing the solvent to form a lipid film;
(4) Adding a buffer solution, and carrying out ultrasonic treatment;
(5) And (5) cleaning.
Further, the solvent used for dissolving in the step (1) is chloroform.
Further, the mass ratio of the oleic acid modified ferroferric oxide nanoparticles, 3,3',5,5' -tetramethylbenzidine, distearoylphosphatidylethanolamine-polyethylene glycol and distearoylphosphatidylethanolamine-polyethylene glycol to the targeting cell-penetrating peptide cRGD in the step (1) is 0.5-2; preferably 1.
Further, the buffer added in step (4) is a phosphate buffer of pH4.5-9.0, preferably pH 7.4.
Further, in the steps (2) and (4), ultrasonic treatment is carried out for 10-40 minutes.
Further, the sonication in step (2) was carried out for 30 minutes, and the sonication in step (4) was carried out for 20 minutes.
Further, trichloromethane is removed by rotary evaporation in step (3).
Further, in step (5), washing is performed by centrifugation.
In another aspect, the present application provides the use of the nanoenzyme or the nanoenzyme prepared by the method in tumor diagnosis and treatment.
Further, a hydrogen peroxide responsive photoacoustic signal is enhanced in the tumor diagnosis.
Further, the tumor therapy is a photochemical kinetic therapy.
Oleic acid-modified ferroferric oxide nanoparticles in the material used in the present application were synthesized according to reported procedures (e.g., cancer Biol Med 2016. Doi. A preferred synthesis procedure is to dissolve 0.76 g of ferric acetylacetonate, 1.69g of oleic acid, 1.60g of oleylamine, and 2.58g of hexadecanediol in 20mL of benzyl ether to obtain a mixture A. The reaction was held at 120 ℃ for 2 hours; subsequently, the temperature was raised to 200 ℃ over 30 minutes and then maintained for 30 minutes. Subsequently, the temperature was increased to 300 ℃ over 30 minutes, followed by a further 30 minutes; when cooled to room temperature, the reaction was washed three times with ethanol and n-hexane. The washed final product was finally dissolved in tetrahydrofuran and stored at-20 ℃. Other methods that can accomplish similar modifications can also be used.
Has the advantages that:
according to the invention, the oleic acid modified ferroferric oxide nanoparticles, 3,3',5,5' -tetramethylbenzidine are encapsulated by distearoyl phosphatidyl ethanolamine-polyethylene glycol, distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD, the hydrophilic modification of the ferroferric oxide nanoparticles is realized, the biocompatibility of the ferroferric oxide nanoparticles is improved, the in vivo circulation time is effectively prolonged, and the dual targeting effect of the targeted cell-penetrating peptide cRGD and magnetic targeting effectively enhances the enrichment effect of the prepared nanoenzyme on tumors.
Under the action of hydrogen peroxide, the double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme encapsulated by distearoyl phosphatidyl ethanolamine-polyethylene glycol, distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD provided by the invention releases iron ions and ferrous ions in an acidic microenvironment, and the released iron ions and ferrous ions can generate Fenton reaction with hydrogen peroxide highly expressed in a tumor microenvironment to generate hydroxyl radicals. The generated hydroxyl free radicals react with 3,3',5,5' -tetramethyl benzidine entrapped in the double-target photochemical kinetic diagnosis and treatment integrated nano enzyme to generate oxidized 3,3',5,5' -tetramethyl benzidine. The produced oxidized 3,3',5,5' -tetramethylbenzidine has strong light absorption in the near infrared region, can be used as a photoacoustic imaging contrast agent, kills tumor cells under the photothermal condition, and performs tumor specific photothermal therapy. In addition, the released iron ions and ferrous ions continuously generate Fenton reaction with hydrogen peroxide highly expressed in a tumor microenvironment to continuously generate hydroxyl free radicals, so that tumor cells are killed, and the chemokinetic treatment of tumors is realized. The combined use of tumor-specific photothermal therapy and chemokinetic therapy realizes photochemical kinetic therapy and accurate and complete tumor treatment.
The invention provides a synthesis method of diagnosis and treatment integrated nano enzyme generating photoacoustic signals through hydrogen peroxide response, wherein the synthesized diagnosis and treatment integrated nano enzyme can be used as a photoacoustic imaging contrast agent through oxidized 3,3',5,5' -tetramethylbenzidine generated under the action of hydrogen peroxide, and the process depends on the characteristics of high hydrogen peroxide expression and a tumor acid microenvironment in a tumor microenvironment, so that the specific identification of tumors is realized, and a new strategy for tumor diagnosis is provided.
Drawings
FIG. 1 is an electron microscope image of the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1;
FIG. 2 is a graph showing the distribution of the particle size of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1;
FIG. 3 is a hysteresis curve diagram of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1;
FIG. 4 is a graph of the absorption spectrum and absorbance at 650 nm of the hydrogen peroxide-responsive dual-targeted photochemical kinetic integrative nanoenzyme co-incubated with hydrogen peroxide at different pH values obtained in example 1;
FIG. 5 is a graph of the absorption spectrum and absorbance at 650 nm of the hydrogen peroxide-responsive dual-targeted photochemokinetic diagnosis and treatment integrated nanoenzyme obtained in example 1 after co-incubation with different concentrations of hydrogen peroxide;
FIG. 6 is photo-acoustic image and photo-acoustic spectrum of hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1 after co-incubation with hydrogen peroxide;
FIG. 7 is a graph showing temperature changes of hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme solution obtained in example 1 at different times before and after laser irradiation;
FIG. 8 is photo acoustic images of the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nano-enzyme solution obtained in example 1 injected systemically and taken in different targeting manners before and 24 hours after injection;
FIG. 9 shows the photo-acoustic intensity of the hydrogen peroxide-responsive dual-targeted photochemokinetic diagnosis and treatment integrated nanoenzyme solution obtained in example 1 injected systemically and 24 hours after injection in different targeting ways;
fig. 10 shows the temperature changes before and after injecting the hydrogen peroxide-responsive double-targeted photochemical kinetics diagnosis and treatment integrated nanoenzyme solution or phosphate buffer solution obtained in example 1 in a systemic administration manner and 24 hours after injection, and after irradiating the tumor site with infrared thermal imager images and laser light in different targeting manners;
FIG. 11 is a statistical graph of tumor volume and post-treatment tumor mass during in vivo photochemical kinetic tumor treatment with hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzymes obtained in example 1.
Detailed Description
The technical solutions in the embodiments of the present invention will be described below with reference to the contents in the embodiments of the present invention. The described embodiments are only some embodiments of the invention, and not all embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.
Example 1 preparation of 16-nm Hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme
Distearoylphosphatidylethanolamine-polyethylene glycol, distearoylphosphatidylethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD was purchased from Sienna Ruixi Biotech, inc.;
oleic acid-modified ferroferric oxide nanoparticles were synthesized according to reported procedures (Cancer Biol Med 2016. Doi. Specifically, 0.76 g of ferric acetylacetonate, 1.69g of oleic acid, 1.60g of oleylamine and 2.58g of hexadecanediol were dissolved in 20mL of benzyl ether to obtain a mixed solution A. The reaction was held at 120 ℃ for 2 hours; subsequently, the temperature was raised to 200 ℃ over 30 minutes and then maintained for 30 minutes. Subsequently, the temperature was increased to 300 ℃ over 30 minutes, followed by a further 30 minutes; when cooled to room temperature, the reaction was washed three times with ethanol and n-hexane. The washed final product was finally dissolved in tetrahydrofuran and stored at-20 ℃.
Step 1, adding oleic acid modified ferroferric oxide nanoparticles, 3,3',5,5' -tetramethylbenzidine, distearoylphosphatidylethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD into chloroform to obtain transparent liquid A, wherein the mass ratio of the oleic acid modified ferroferric oxide nanoparticles, 3,3',5,5' -tetramethylbenzidine, distearoylphosphatidylethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD is 1.1;
step 2, carrying out ultrasonic treatment on the solution A for 30 minutes in a water bath at normal temperature;
step 3, transferring the solution A into a round-bottom flask, and removing trichloromethane by using a rotary evaporator under the condition of water bath at 45 ℃ to form a lipid membrane;
step 4, adding a phosphate buffer solution into the round-bottom flask with the formed lipid membrane under the ultrasonic condition, and carrying out ultrasonic treatment for 20 minutes by using a water bath;
and 5, washing the nano particles by a centrifugal method to remove redundant lipid.
As shown in fig. 1, the morphology characterization data of the hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in this example is shown. Wherein the left image is an electron microscope image of the hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme obtained by adopting a field emission transmission electron microscope test. The right image is a high-resolution electron microscope image of the hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme obtained by adopting a high-resolution field emission transmission electron microscope test. As can be seen from the left figure of FIG. 1, the particle size distribution of the obtained hydrogen peroxide response double-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme is uniform. As can be seen from the right graph of FIG. 1, the crystallinity of the lattice parameter of the obtained hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme is about 0.26 nm and conforms to the (3 1) plane of the ferroferric oxide nanocrystal.
FIG. 2 is a particle size distribution diagram of a double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme with hydrogen peroxide response obtained by a dynamic light scattering method. The average particle size of the obtained hydrogen peroxide-responsive double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme is 17 +/-1 nanometers, the particle size distribution is concentrated, the particle size of the nano molecular probe used for passive tumor aggregation is met, and the hydrogen peroxide-responsive double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme is beneficial to being enriched in tumor tissues through the permeation and retention Effect (EPR) of the tumor tissues.
Fig. 3 is a hysteresis curve of hydrogen peroxide-responsive double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme and oleic acid-modified ferroferric oxide measured by a vibrating sample magnetometer, which shows that the obtained hydrogen peroxide-responsive double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme maintains a magnetization state, and thus magnetic targeting is possible.
Example 2 pH value response Performance test
Hydrogen peroxide solution is added into the hydrogen peroxide-responsive double-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution with different pH values obtained in the example 1 for incubation, and after full reaction, an ultraviolet visible near-infrared spectrophotometer is adopted to measure the absorption spectrum of the nano enzyme solution.
FIG. 4 is the pH value response performance characterization data of the hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme obtained in example 1. The left graph shows an absorption spectrum of the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme with different pH values, which is obtained by measuring with an ultraviolet-visible near-infrared spectrophotometer, incubated with a hydrogen peroxide solution, and the right graph shows an absorbance value at 650 nm before and after the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme with different pH values is incubated with the hydrogen peroxide solution. As can be seen from FIG. 4, the obtained hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme has good response performance to pH value.
Example 3 Hydrogen peroxide response Performance test
Hydrogen peroxide solutions with different concentrations are added into the hydrogen peroxide-responsive double-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution obtained in the example 1 for incubation, and after full reflection, an ultraviolet visible near-infrared spectrophotometer is adopted to measure the absorption spectrum of the hydrogen peroxide-responsive double-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution.
FIG. 5 is the hydrogen peroxide response performance characterization data of the hydrogen peroxide response dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1. The left graph shows the absorption spectrum of the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme co-incubated with hydrogen peroxide solutions of different concentrations, which is measured by an ultraviolet-visible near-infrared spectrophotometer, and the right graph shows the absorbance value at 650 nm before and after the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme co-incubated with the hydrogen peroxide solutions of different concentrations. As can be seen from FIG. 5, the obtained hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme has good response performance to hydrogen peroxide, and the absorbance value at 650 nm has a good linear relationship with the hydrogen peroxide concentration.
Example 4 in vitro photoacoustic Performance testing
Hydrogen peroxide solution is added into the hydrogen peroxide-response double-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution obtained in example 1 for co-incubation, the solution is transferred into a polytetrafluoroethylene tube with the inner diameter of 0.30 mm and the outer diameter of 0.60 mm after being fully reflected, and photoacoustic intensities at 680 nm and 990 nm are measured by adopting a photoacoustic tomography imaging system.
Fig. 6 is in-vitro photoacoustic performance test data of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1. The upper graph is photoacoustic images before and after the hydrogen peroxide solution is added into the hydrogen peroxide solution for co-incubation of the hydrogen peroxide-responsive dual-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution, and the lower graph is photoacoustic spectra at 680 nanometers and 990 nanometers before and after the hydrogen peroxide solution is added into the hydrogen peroxide solution for co-incubation of the hydrogen peroxide-responsive dual-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution. As can be seen from fig. 6, the obtained hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme has good photoacoustic imaging performance, and the photoacoustic performance of the hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme is related to hydrogen peroxide.
Example 5 in vitro photothermal Performance test
Hydrogen peroxide solution is added into the hydrogen peroxide-responsive double-target photochemical kinetics diagnosis and treatment integrated nano enzyme solution obtained in the example 1 for incubation, a laser with the wavelength of 808 nanometers and 1 watt per square centimeter is used for irradiation after the full reaction, and the temperature of the solution is measured by a near infrared imager.
FIG. 7 is the in vitro photothermal performance test data of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1. As can be seen from fig. 6, the obtained hydrogen peroxide-responsive dual-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme has good photothermal imaging performance, and the obtained hydrogen peroxide-responsive dual-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme has good photothermal stability.
Example 6 tumor detection Performance test
Nude mice bearing 4T1 tumors were anesthetized with oxygen containing 2% isoflurane. The hydrogen peroxide-responsive double-targeted photodynamic therapy and diagnosis integrated nanoenzyme solution (200. Mu.L, 10 mg/kg) obtained in example 1 was injected by systemic administration or replaced by distearoylphosphatidylethanolamine-polyethylene glycol in an equal amount during the preparation process instead of distearoylphosphatidylethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD (200. Mu.L, 10 mg/kg). And one group of nude mice was treated with magnet after injection to simulate magnetic targeting. And (3) imaging by adopting a photoacoustic imaging system before and 24 hours after injection to obtain photoacoustic images of the injection.
Fig. 8 and 9 are tumor detection performance test data of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1. Fig. 8 is photoacoustic images of a tumor region in the photoacoustic images before and 24 hours after the hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme solution obtained in example 1 is injected by systemic administration, and fig. 9 is photoacoustic intensity of the tumor region in the photoacoustic images before and 24 hours after the hydrogen peroxide-responsive dual-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme solution obtained in example 1 is injected by systemic administration. As can be seen from fig. 8 and 9, 24 hours after the hydrogen peroxide-responsive double-targeted photochemical kinetic diagnosis and treatment integrated nanoenzyme solution obtained in example 1 was systemically administered, the tumor area of the biological/physical double active targeting group had the highest photoacoustic intensity (80.02 ± 9.50), which was 1.71 times that of the biological active targeting group alone (46.70 ± 2.26), and 2.99 times that of the non-active targeting group (26.80 ± 1.92).
The reaction between the hydrogen peroxide-responsive double-targeted photochemical dynamic diagnosis and treatment integrated nanoenzyme obtained in the example 1 and hydrogen peroxide in a tumor environment is shown to form oxidized 3,3',5,5' -tetramethylbenzidine, and the hydrogen peroxide-responsive double-targeted photochemical dynamic diagnosis and treatment integrated nanoenzyme obtained in the example 1 has good tumor detection performance. In addition, the delivery efficiency of the nanoenzyme is effectively improved by biological/physical double active targeting.
Example 7 in vivo photothermal Property test
Mice bearing subcutaneous 4T1 xenograft tumors were injected with the same volume of hydrogen peroxide-responsive dual-targeted photochemokinetic integrated nanoenzyme solution or phosphate buffer obtained in example 1, respectively, by systemic administration. And one group of nude mice was treated with magnet after injection to simulate magnetic targeting. The tumor site was irradiated with 808 nm near-infrared laser at a power density of 2 watts/cm 24 hours after injection, and the temperature change before and after laser irradiation was recorded with a thermal infrared imager.
FIG. 10 shows in vivo photothermal performance test data of the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nanoenzyme obtained in example 1. The upper graph is the infrared thermal imager pictures before laser irradiation and after laser irradiation for different times after injecting the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme solution obtained in the embodiment 1 and carrying out magnet treatment, only the hydrogen peroxide-responsive double-targeting photochemical kinetic diagnosis and treatment integrated nano enzyme solution obtained in the embodiment 1 and 24 hours after injecting the phosphate buffer solution, and the lower graph is the temperature change after the tumor part is irradiated by the laser. As can be seen from fig. 10, the tumor surface temperature of the mice injected with the hydrogen peroxide-responsive dual-targeted photodynamic therapy and diagnosis integrated nanoenzyme solution obtained in example 1 and treated with magnet rapidly increased from about 35 degrees celsius to about 61.7 degrees celsius under laser irradiation, the tumor surface temperature of the mice injected with only the hydrogen peroxide-responsive dual-targeted photodynamic therapy and diagnosis integrated nanoenzyme solution obtained in example 1 rapidly increased from about 35 degrees celsius to about 45.3 degrees celsius under laser irradiation, and the tumor surface temperature of the mice injected with the same volume of phosphate buffer solution showed only slight changes under laser irradiation, indicating that the hydrogen peroxide-responsive dual-targeted photodynamic therapy and diagnosis integrated nanoenzyme obtained in example 1 has good in vivo photothermal properties. In addition, the biological/physical double active targeting effectively improves the delivery efficiency and the photothermal treatment effect of the nanoenzyme.
Example 8 in vivo photochemical kinetic tumor treatment assay
Mice carrying subcutaneous 4T1 xenograft tumors were divided into 6 groups, including a control group, a laser group, a nanoenzyme + laser group, a nanoenzyme + magnetic targeting + laser group. For the "nanoenzyme" group, the hydrogen peroxide-responsive dual-targeted photodynamic theranostic nanoenzyme solution (200 μ l, 10 mg/kg) obtained in example 1 was injected by repeated systemic administration on days 0, 3, 6 and 9. For the "magnetic targeting" group, an external magnetic field was applied at its tumor site 24 hours after each systemic administration. For the "laser" group, the tumor site was irradiated with a near-infrared laser at 808 nm for 10 minutes at a power density of 2 watts/cm 24 hours after the first systemic administration. For the non "nanoenzyme" group, systemic administration injection of 200 μm phosphate buffer was repeated on days 0, 3, 6 and 9. In addition, tumor volume was monitored every two days and mice were sacrificed on day 13, tumors were removed and weighed to assess the effect of the synergistic treatment effect.
FIG. 11 shows the in vivo photochemodynamic tumor therapy data of hydrogen peroxide-responsive dual-targeting photochemodynamic diagnosis and treatment integrated nanoenzymes obtained in example 1. Wherein the left panel is the tumor volume during treatment of mice from different treatment groups. The right panel shows the tumor mass of mice in different treatment groups after treatment. As can be seen from fig. 11, on day 13 after treatment, the tumor volumes of the nanoenzyme group (930.57 ± 313.71), the nanoenzyme + laser group (928.64 ± 269.69), the nanoenzyme + magnetic targeting group (599.12 ± 165.62) and the nanoenzyme + magnetic targeting + laser group (27.61 ± 61.74) were 75.66%, 75.48%, 48.69% and 2.24% of the control group (1230.38 ± 258.81), respectively. The tumor inhibition rate of the photochemical kinetic therapy is about 97.76 percent, which is about 4 times higher than that of the simple photothermal therapy or the chemical kinetic therapy. The results show that the mice treated by the nano enzyme magnetic targeting and the laser show the strongest tumor inhibition effect, and the photochemical kinetics have obvious anti-tumor treatment effects. In addition, the biological/physical double active targeting effectively improves the delivery efficiency and the treatment effect of the nanoenzyme.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and should not be taken as limiting the scope of the present invention, which is intended to cover any modifications, equivalents, improvements, etc. within the spirit and scope of the present invention.

Claims (10)

1. The hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nanoenzyme is characterized by consisting of oleic acid modified ferroferric oxide nanoparticles and 3,3',5,5' -tetramethylbenzidine molecules, wherein distearoylphosphatidylethanolamine-polyethylene glycol molecules and distearoylphosphatidylethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD molecules are modified on the surface of the nanoenzyme.
2. The nanoenzyme of claim 1, wherein the nanoenzyme has an average particle size of 16 nanometers.
3. The method for preparing nanoenzyme according to claim 1, comprising:
(1) Dissolving ferroferric oxide nano-particles modified by oleic acid, 3,3',5,5' -tetramethyl benzidine, distearoyl phosphatidyl ethanolamine-polyethylene glycol-targeted cell-penetrating peptide cRGD;
(2) Carrying out water bath ultrasonic treatment;
(3) Removing the solvent to form a lipid film;
(4) Adding a buffer solution, and carrying out ultrasonic treatment;
(5) And (5) cleaning.
4. The production process according to claim 3, wherein the solvent used for the dissolution in the step (1) is chloroform.
5. The preparation method according to claim 3, wherein the mass ratio of the oleic acid-modified ferroferric oxide nanoparticles, 3,3',5,5' -tetramethylbenzidine, distearoylphosphatidylethanolamine-polyethylene glycol-targeting cell-penetrating peptide cRGD in step (1) is 0.5-2; preferably 1.
6. The method according to claim 3, wherein the buffer added in step (4) is a phosphate buffer of pH4.5-9.0, preferably pH 7.4.
7. The method according to claim 3, wherein the sonication in steps (2), (4) is carried out for 10-40 minutes.
8. The production method according to claim 3, wherein the ultrasonication in step (2) is carried out for 30 minutes, and the ultrasonication in step (4) is carried out for 20 minutes.
9. The process according to claim 4, wherein chloroform is removed by rotary evaporation in the step (3).
10. Use of the nanoenzyme according to claim 1 or 2 or prepared using the method according to claims 2-9 in the diagnosis and treatment of tumors.
CN202211258437.6A 2022-10-14 2022-10-14 Hydrogen peroxide response double-targeting photochemical kinetics diagnosis and treatment integrated nano enzyme Pending CN115531561A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200030462A1 (en) * 2018-07-24 2020-01-30 Indian Institute Of Technology, Indore GREEN SYNTHESIS OF BIOCOMPATIBLE AND NEAR INFRARED ACTIVE EUGENATE (4-allyl-2-methoxyphenolate) CAPPED IRON OXIDE NANOPARTICLES FOR DEEP TISSUE IMAGING AND THERAPY
CN114732796A (en) * 2022-02-18 2022-07-12 北京大学第三医院（北京大学第三临床医学院） Double-targeting drug-loaded microbubble and preparation method and application thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20200030462A1 (en) * 2018-07-24 2020-01-30 Indian Institute Of Technology, Indore GREEN SYNTHESIS OF BIOCOMPATIBLE AND NEAR INFRARED ACTIVE EUGENATE (4-allyl-2-methoxyphenolate) CAPPED IRON OXIDE NANOPARTICLES FOR DEEP TISSUE IMAGING AND THERAPY
CN114732796A (en) * 2022-02-18 2022-07-12 北京大学第三医院（北京大学第三临床医学院） Double-targeting drug-loaded microbubble and preparation method and application thereof

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHAOYI CHEN ET AL: "Dual-targeting nanozyme for tumor activatable photo-chemodynamic theranostics", 《JOURNAL OF NANOBIOTECHNOLOGY》, vol. 20 *
HUANHUAN WU ET AL: "Fe3O4-Based Multifunctional Nanospheres for Amplified Magnetic Targeting Photothermal Therapy and Fenton Reaction", 《ACS BIOMATERIALS SCIENCE & ENGINEERING》, vol. 5, pages 1 *
ZHAOYU MA ET AL: "In Situ Nanozyme-Amplified NIR-II Phototheranostics for Tumor-Specific Imaging and Therapy", 《ADVANCED FUNCTIONAL MATERIALS》, vol. 31 *
刘卫等主编: "《经皮给药纳米技术》", 30 November 2020, 中国医药科技出版社, pages: 262 *

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