CN115518154B - FeCuNC nano material, preparation and application thereof - Google Patents
FeCuNC nano material, preparation and application thereof Download PDFInfo
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Abstract
The invention belongs to the field of biomedicine. In particular to a FeCuNC nano material, and preparation and application thereof. The invention discovers that FeCuNC has strong photo-thermal effect and rich pseudo-enzyme activity. The photo-thermal effect can further accelerate the decomposition of the hydrogen peroxide which is over-expressed in the tumor to generate rich active oxygen, and can realize the chemical kinetics and photo-thermal synergistic treatment, induce the apoptosis of cancer cells and inhibit the growth of the tumor.
Description
Technical Field
The invention belongs to the technical field of development of anticancer nano materials, and relates to a FeCuNC nano material and a preparation method thereof, and application thereof in preparation of a photo-thermal treatment and chemical kinetics treatment combined anticancer drug based on photo-thermal effect and simulated enzyme activity.
Background
Cancer remains one of the most serious diseases in humans, and thus development of efficient anticancer medical strategies is urgent. To date, conventional single mode therapies still suffer from poor bioavailability, impaired target specificity, systemic and organ toxicity, and the like. Combination therapy is one of the most promising approaches to address these problems due to its high efficacy and low risk of relapse. Early combination therapies included lipid and polymer nanocapsules, two or three drugs, but their performance was largely dependent on the drug carrying capacity of the different drugs. To date, there has been increasing interest in new medical applications of two-dimensional nanomaterials with extraordinary physicochemical properties, developing two-dimensional nanomedicines for multimodal nanomedicineResearch on vectors has proliferated. For example graphene, moO x ，WS 2 And MoS 2 Have been used to construct a combination therapy platform that exhibits outstanding performance in cancer therapy. However, developing new strategies for synergistic combination therapies with multifunctional two-dimensional nanomaterials with higher loading capabilities remains a major challenge.
Hydrogen peroxide (H) 2 O 2 ) Plays an important role in many physiological and pathological processes, in particular H associated with a variety of cancers 2 O 2 With imbalance, reactive oxygen species (ROS, including singlet oxygen, superoxide anions, and hydroxyl radicals) can be generated, causing oxidative damage to cancer cells. Nano-catalyst participated chemical kinetics therapy (CDT) can catalyze H in tumor microenvironment through biomimetic catalysis process 2 O 2 Converts into ROS with strong toxicity. The nanocarbon suspension is an important nano-marker for clinical diagnosis of lymph node biopsies, and carbon materials show great potential in Infrared (IR) thermal imaging and photothermal therapy (PTT) due to the effectiveness of their photothermal properties. Therefore, a well-defined diatomic site located on the optimized structure of the carbon nanoparticles is expected to become an effective activation H 2 O 2 To facilitate high-precision diagnosis and ablation of metastatic sentinel nodes (SLNs).
Disclosure of Invention
In order to realize efficient identification and treatment of tumors at lymph nodes, hydrogen peroxide at the tumor microenvironment is fully utilized, and the problems of poor biological safety, poor drug resistance, single functionality and the like of the traditional anti-tumor nano material are solved. The primary aim of the invention is to provide a FeCuNC nano material which is a hollow nitrogen doped carbon nano sphere and has Fe and Cu active sites. The material can be used for preparing antitumor drugs; aims to realize the combination of photothermal therapy and chemical kinetic therapy with anticancer drugs and the identification of sentinel lymph node metastasis, and effectively inhibit tumor metastasis and recurrence.
The hydration diameter of the FeCuNC nano material is 100-300 nm.
The second object of the present invention is to provide a method for preparing FeCuNC nanomaterial, comprising the steps of:
adding tetraethyl orthosilicate into the mixed solution of ammonia water and absolute ethyl alcohol or propanol to obtain a template SiO 2 The method comprises the steps of carrying out a first treatment on the surface of the Adding Dopamine (DA) water solution into the mixed solution, continuously stirring, then adding ferric acetylacetonate (II) or ruthenium acetylacetonate, continuously stirring, and then centrifugally washing and drying to obtain Fe-PDA-SiO 2 ；Fe-PDA-SiO 2 Annealing in a protective atmosphere to obtain FeNC; uniformly mixing FeNC, urea and copper (II) phthalocyanine (CuPc), and then annealing in a protective atmosphere to obtain the FeCuNC nano material.
Further, the preparation method of the FeCuNC nano material,
the concentration of ammonia in the starting solution is 15-35 wt%.
The volume ratio of the ammonia water to the absolute ethyl alcohol or the propanol is 1: 20-1: 40.
tetraethyl orthosilicate, ammonia water and absolute ethyl alcohol or propanol, wherein the volume ratio of the tetraethyl orthosilicate to the absolute ethyl alcohol or propanol is 1: 15-1: 30.
the concentration of the dopamine solution is 2-5wt%; the volume ratio of the dopamine solution to the mixed solution is 1:5 to 1:8.
the mass ratio of the ferric acetylacetonate (II) or the ruthenium acetylacetonate to the dopamine is 1:1.5 to 1:3.
Fe-PDA-SiO 2 annealing the powder in nitrogen, and heating up at 3-8 ℃ for min -1 The method comprises the steps of carrying out a first treatment on the surface of the The annealing temperature is 700-800 ℃ and the annealing time is 1.5-2.5 h.
Fenc, urea and copper (II) phthalocyanine, mass ratio 1:40:0.25 to 1:60:0.3.
uniformly mixing FeNC, urea and copper (II) phthalocyanine, annealing in nitrogen, and heating at a temperature of 2.5-3.5 ℃ for min -1 The method comprises the steps of carrying out a first treatment on the surface of the The annealing temperature is 550-650 ℃, and the annealing time is preferably 1.5-2.5 h.
The third purpose of the invention is to provide the application of the FeCuNC nano material in decomposing hydrogen peroxide to generate active oxygen or in preparing a preparation for decomposing hydrogen peroxide to generate active oxygen.
Further, the FeCuNC nano material can accelerate the decomposition of hydrogen peroxide and enhance the generation of active oxygen by the irradiation of near infrared II region light.
Further, the illumination power is 0.5-2.2W cm -2 The illumination time is 0.5-10 min, and the concentration of the illumination treatment is 0.5-50 ppm.
Further preferably, the power of the illumination is 1.2 to 2.0W cm -2 The illumination time is 2-5 min, and the illumination treatment concentration is 10-40 ppm.
Further, mixing FeCuNC with the target modifier, stirring, and centrifugally washing to obtain the FeCuNC@CM nanosphere target material; preferably, the targeting modifier is an extracted cell membrane, including cancer cell membrane, white blood cell membrane; in the mixed system solution, the concentration ratio of FeCuNC to cell membrane is 0.5-2.
The target receptor is protein, and the targeting of different cancer cells is realized according to different cell membrane surface active molecules.
The fourth object of the invention is to provide the application of the FeCuNC nano material in preparing antitumor drugs; in particular to the application of photo-thermal enhanced antitumor drugs.
The fifth object of the present invention is to provide an antitumor drug comprising the FeCuNC nanomaterial.
The FeCuNC nano material provided by the invention has catalase mimic enzyme activity.
Further, the FeCuNC nanomaterial also has peroxidase mimic enzyme activity, which is capable of catalyzing H 2 O 2 Active oxygen is generated, and chemical kinetics treatment is realized.
Further, the FeCuNC nanomaterial can generate heat by irradiation of near infrared II region light; preferably, the power of illumination is 0.5-2.2W cm -2 The illumination time is 0.5-10 min, and the concentration during illumination treatment is 0.5-50 ppm.
Further, the FeCuNC nanomaterial can accelerate the decomposition of hydrogen peroxide by irradiation of near infrared II region light, and enhance the generation of active oxygen, thereby being used for synergistic chemical kinetics treatment; preferably, the power of illumination is 1.2-2.0W cm -2 The illumination time is 2-5 min, and the illumination treatment time isThe concentration is 10-40 ppm, and the concentration of hydrogen peroxide is 0.05-50 mM.
Further, the FeCuNC nanomaterial can generate heat by irradiation of near infrared II region light, and has certain light irradiation cycle heat generation capacity; the power of the illumination cycle is 1-2.2W cm -2 The illumination time is 40-200 min, and the concentration during illumination treatment is 10-50 ppm.
The FeCuNC nano material is used for preparing an anti-tumor drug, has excellent anti-tumor activity, and can effectively kill tumor cells and ablate tumors; can realize the identification of sentinel lymph node metastasis and inhibit tumor metastasis and recurrence.
The research of the invention discovers that the FeCuNC material with nanometer size can effectively generate active oxygen under the condition of no illumination.
The research of the invention discovers that the material prepared by the preparation method has better biocompatibility, better photo-thermal promotion of active oxygen release and stronger simulated enzyme activity, and better tumor effect.
The neoplasm of the invention may be benign and/or malignant.
The invention applies drug to mice by tail vein injection.
For example, in the use process, physiological saline can be used for dispersing FeCuNC@CM nanospheres; the resulting dispersion solution was then administered by intravenous injection. The preferred dosage of the medicine is 1.5-3 mg kg 1 . Each dosing subject (e.g., a mouse) preferably applies a dose of 50ug of hollow fecunc@cm nanospheres.
Preferably, the FeCuNC@CM nanomaterial is not lower than a pharmaceutically effective amount; preferably, the composition further comprises pharmaceutically acceptable auxiliary materials; preferably, it is in any pharmaceutically acceptable dosage form; preferably, a pharmaceutically acceptable injectable formulation; further preferred are pharmaceutically acceptable topical injectable formulations.
The research of the invention discovers that FeCuNC@CM nano material can promote the formation of active oxygen in tumor cells in a mode of Yu Guangre; in addition, the FeCuNC@CM nanomaterial has good propertiesFor example, it has good peroxidase activity, catalyzes H 2 O 2 Active oxygen is produced.
According to the research of the invention, the FeCuNC@CM nanomaterial can catalyze hydrogen peroxide to generate active oxygen in situ at a tumor tissue by photo-thermal promotion and synergy with chemical kinetics treatment, so that the active oxygen content at the biological tissue is improved. Compared with the traditional medicine molecules, feCuNC@CM is recycled to generate active oxygen, so that the medicine property of the medicine is improved. Secondly, the FeCuNC@CM nano material has good biocompatibility, so that the FeCuNC@CM nano material has good biological safety on treatment of mouse breast cancer.
The beneficial effects are that:
(1) The developed FeCuNC@CM nano material has good anti-tumor activity;
(2) The developed FeCuNC@CM nano material achieves the effects of killing tumor cells and improving the anti-tumor effect through a photo-thermal combined chemical kinetics reaction mechanism;
for example, fecunc@cm nanomaterials are capable of catalyzing hydrogen peroxide in situ at tumor tissue to generate reactive oxygen species in vivo through photothermal promotion and in conjunction with chemokinetic treatment, thereby increasing the reactive oxygen species content at the biological tissue. Enhancing active oxygen content, and oxidizing to kill tumor cells.
In addition, the FeCuNC@CM nano material has good biocompatibility, so that the FeCuNC@CM nano material has good biological safety for treating the breast cancer of a mouse.
(3) The developed FeCuNC@CM nano material realizes the identification of sentinel lymph node metastasis through the carbon sphere imaging function of the carbon suspension, and can realize primary treatment of metastatic lymph nodes through cell membrane targeting and photo-thermal combination, thereby effectively inhibiting metastasis and recurrence of tumors.
(4) The FeCuNC@CM nano material has the advantages of simple preparation method, mild reaction conditions, low cost and wide application prospect, and can be prepared in a large scale.
Drawings
FIG. 1 is a Transmission Electron Microscope (TEM) image, X-ray diffraction (XRD) image, high Resolution Transmission Electron Microscope (HRTEM) image and radiation energy spectrum (EDS) distribution diagram of the hollow nitrogen doped carbon nanosphere FeCuNC nanomaterial prepared in example 1;
wherein (a) is a TEM image; (b) is an XRD pattern; (c) is an HRTEM image; (d) is an EDS profile.
FIG. 2 shows the photo-thermal effect of hollow FeCuNC nanomaterial and the results of simulated enzyme detection;
(a) To detect a simulated peroxidase activity pattern; (b) detecting photo-thermal effect graphs of different FeCuNC concentrations; and (c) detecting a FeCuNC photo-thermal effect graph under different powers.
FIG. 3 is a cell-level antitumor effect study;
(a) A FeCuNC endocytic effect diagram of different time cells; (b) Incubating the cell viability map of the different cell types for 24 hours under FeCuNC treatment; (c) Fluorescence images of intracellular active oxygen stained by DCFH-DA after different treatments; (d) After different treatments, the flow treatment result of the intracellular active oxygen dyed by DCFH-DA; (e) Following different treatments, mice breast cancer cells 4T1 were incubated for 24h for cell viability;
control, NC, NC+H in FIG. 3 2 O 2 ，FeNC，FeNC+H 2 O 2 ，FeCuNC，FeCuNC+H 2 O 2 ,FeCuNC+Laser，FeCuNC+H 2 O 2 The +lasers are all products of cell membrane targeting modifiers.
FIG. 4 is a study of tumor treatment effect in vivo at the animal level;
(a) Is a weight chart of mice under different conditions and at different time; (b) Tumor volume maps of mice at different times under different conditions; (c) is a visual image of the tumor of the mouse on day 18 under different conditions; (d) The temperature rise effect diagram is a graph of different photo-thermal time in the mouse under different conditions; (e) Graph of photo-thermal different time temperature rise in mice under different conditions.
Detailed description of the preferred embodiments
The invention will be further illustrated with reference to specific examples. These examples should be construed as merely illustrative of the present invention and not limiting the scope of the present invention. Various changes or modifications to the invention based on the principles of the invention will also fall within the scope of the appended claims after reading the description of the invention.
Example 1
Preparation of hollow FeCuNC@CM nanospheres:
ethanol (70 mL), H 2 O(10mL)、NH 3 ·H 2 O (3 mL,30 wt%) was mixed and stirred for 10 minutes. Then, tetraethyl orthosilicate (3.5 mL) was added and stirred for another 15min. 10mL of an aqueous solution containing 0.5g of dopamine was added and stirred for 6h. Then 254mg of iron (II) acetylacetonate was added thereto and stirred for another 12 hours. Product Fe-PDA-SiO 2 Centrifuging, washing with ethanol for 3 times, and drying at 70deg.C. Fe-PDA-SiO 2 At 5℃for a min under nitrogen –1 Is annealed at 750 ℃ for 2 hours. Then, the resulting black powder was washed with HF (10%) for 24h to give FeNC. Then, 20mg of Fenc, 1g of urea and 5mg of copper (II) phthalocyanine (CuPc) were ground and pulverized, and mixed uniformly. Then at N 2 In atmosphere at 3deg.C for min –1 Annealing at 600℃for 2 hours to give FeCuNC, and subjecting FeCuNC (1 mL,1mg mL –1 ) And extracted 4T1-Luc cell membrane (10. Mu.L, 10mg mL) –1 ) Mixing, stirring for 12h, and centrifugally washing to obtain FeCuNC@CM.
From fig. 1 (a), (c) and (d), feCuNC nanospheres are known to be uniform hollow nitrogen-doped carbon nanospheres.
Example 2
Test of peroxidase activity-mimicking properties of hollow FeCuNC nanospheres (prepared in example 1): the experiments were divided into the following groups:
(1) Unmodified nitrogen-doped carbon Nanospheres (NC); (2) iron-modified nitrogen-doped carbon nanospheres (FeNC); (3) Iron-copper double-site modified nitrogen-doped carbon nanospheres (FeCuNC); 3, '5,5' -tetramethyl benzidine (TMB) was used as probe in HAc-NaAc buffer and H 2 O 2 In the presence of aqueous solution, H was measured 2 O 2 Activation efficiency. FeCuNC, feNC or NC (5. Mu.L, 1mg mL) was added sequentially to HAc-NaAc buffer (100. Mu.L, pH= 3.5,0.1M) –1 )、H 2 O 2 (100. Mu.L, 100 mM) aqueous solution and TMB (100. Mu.L, 1 mM) alcoholic solution. The absorbance of the mixed solution at 652nm was recorded with an ultraviolet spectrophotometer.
From fig. 2 (a), it can be seen that FeCuNC nanospheres have the highest ultraviolet absorption intensity, which proves that the FeCuNC nanospheres have the highest capability of generating active oxygen.
Example 3
Test of photo-thermal properties of hollow FeCuNC nanospheres (prepared in example 1):
experiments were divided into two subgroups based on different variable parameters:
(1) FeCuNC temperature rise change with same power and different concentrations
FeCuNC nanospheres with different concentrations are irradiated by 808nm laser for 10min, and the temperature of the FeCuNC nanospheres is monitored and recorded every 30s by a thermal infrared imager (FLIR C2). Wherein the different concentrations include: 0, 10, 17.5, 25, 37.5, 50ppm, power fixed at 1.0W cm –2 。
(2) FeCuNC temperature rise change with same concentration and different power
FeCuNC nanospheres of the same concentration (concentration fixed at 25 ppm) were irradiated with 808nm laser for 10min and the temperature was monitored and recorded every 30s with a thermal infrared imager (FLIR C2). Wherein the different powers include: 0.5,1.0,1.4,1.8,2.2W cm –2 。
From fig. 2 (b), it can be seen that the light effect of FeCuNC nanospheres increases with increasing concentration, the temperature change increases continuously, and the maximum concentration of 50ppm can rise to 25 ℃ within 10 min. From fig. 2 (c), it can be known that the light effect of FeCuNC nanospheres increases with increasing power, the temperature change is continuously increased, and the highest temperature rise change can reach 60 ℃.
Example 4
Detection of uptake ability of hollow fecunc@cm nanomaterial (prepared in example 1) at the cell level: the invention uses rhodamine B (RhB, 1mg mL) -1 1 mL) and FeCuNC (1 mg mL) -1 1 mL) was mixed and stirred overnight, centrifuged at 8000rpm for 10min, the resulting solution was washed and the supernatant clarified to give RhB-modified FeCuNC (RhB-FeCuNC), and 4T1 cells (10 per well) 4 Individual cells) and RhB-FeCuNC (0.025 mg mL -1 100 uL) were incubated in 96-well plates for different times 0, 0.5,1.0 and 2.0h to observe the cellular uptake effects.
From fig. 3a, it can be seen that the fluorescence intensity of intracellular rhodamine B (RhB) gradually increases with time, indicating that fecunc@cm is efficiently endocytosed by 4T1 cells, and that the more nanospheres endocytosed with time.
Example 5
Detection of toxicity at the cellular level of hollow fecunc@cm nanomaterial (prepared in example 1):
experiments were divided into two subgroups based on different variable parameters:
(1) Different cells are incubated for the same time under different cell environments, and cell activity is detected
The invention uses FeCuNC@CM nano material (0, 25, 50, 75, 100 ppm) with different concentrations, cancer cells (mouse breast cancer cells 4T1; human non-small cell lung cancer cells A549) and normal cells (mouse embryo fibroblast 3T3; human umbilical vein endothelial cells HUEVC, mouse epithelial-like fibroblast L929) (each hole is 10) 4 Individual cells, cell purchase Yu Xiangya medical college) for 24h.
From fig. 3 (b), it can be known that after different concentrations of fecunc@cm nanomaterial are incubated with different normal cells for 24 hours, the cell activity does not change significantly, but after the fecunc@cm nanomaterial is incubated with cancer cells for 24 hours, the cell survival rate is reduced to a certain extent, which indicates that the fecunc@cm nanomaterial has no significant cytotoxicity to the normal cells, has good biocompatibility and has a certain killing capacity to the cancer cells.
(2) Incubation of mouse breast cancer cells 4T1 for the same time under different treatment groups of FeCuNC, detection of cell Activity the invention provides different treatment groups at the same concentration (concentration of 25 ppm) with mouse breast cancer cells 4T1 (10 per well) 4 Individual cells, cell purchase Yu Xiangya medical college) for 24h. The different treatment groups are respectively: control, NC@CM, NC@CM+H 2 O 2 ，FeNC@CM，FeNC@CM+H 2 O 2 ，FeCuNC@CM，FeCuNC@CM+H 2 O 2 ,FeCuNC@CM+Laser，FeCuNC@CM+H 2 O 2 +Laser。
H in each of the above groups 2 O 2 The concentration is 50ppm; the illumination conditions of the lasers are 1.0W cm –2 ，5min。
As can be seen from fig. 3 (e), after the nanomaterial and the mouse breast cancer cells of different treatment groups are incubated for 24 hours, the cell activity is obviously changed, and after the nanomaterial and the mouse breast cancer cells are incubated for 24 hours together, the cell viability is reduced to a certain extent, the cytotoxicity of the group of fecunc@cm combined with hydrogen peroxide and light and heat is strongest, which indicates that the killing capacity of chemical kinetics combined with light and heat treatment on the cancer cells is very strong.
Example 6
Detection of the ability of hollow fecunc@cm nanomaterial (prepared in example 1) to generate reactive oxygen species at the cellular level:
the generation of active oxygen in vivo is illustrated from two different aspects:
(1) Qualitative elucidation of the in vivo production of reactive oxygen species
ROS production within cells can be detected using 2',7' -chlorofluorofluorescein diacetate (DCFH-DA). The invention sets 4T1 cells (2×10) 4 perwell) was placed in 24-well plates and incubated for 4h under different conditions. Wherein H is 2 O 2 Is 20mM; the final concentration of NC@CM, feNC@CM and FeCuNC@CM was 25ppm; the illumination power is 0.5W cm -2 The method comprises the steps of carrying out a first treatment on the surface of the The illumination time is 2min; DCFH-DA was mixed with the medium to a final concentration of 20mM.
As can be seen from FIG. 3 (c), the DCFH-DA probe was oxidized by ROS to produce green-emitting 2, 7-Dichlorofluorescein (DCF). Under fecunc@cm conditions, all groups produced green fluorescence. The group with the strongest fluorescence intensity was the group of fecunc@cm combined with hydrogen peroxide and photo-heat, indicating that the chemo-kinetic and photo-thermal treatments produced ROS synergy.
(2) From a quantitative point of view, the generation of active oxygen in vivo was demonstrated
The invention sets 4T1 cells (2×10) 4 perwell) was placed in 24-well plates, and after incubation for 4h under different conditions, all cells were collected by digestion with pancreatin and examined by flow cytometry. Wherein H is 2 O 2 Is 20mM; the final concentration of NC@CM, feNC@CM and FeCuNC@CM was 25ppm; the illumination power is 0.5W cm -2 The method comprises the steps of carrying out a first treatment on the surface of the The illumination time is 2min; DCFH-DA was mixed with the medium to a final concentration of 20mM.
From the flow statistics of fig. 3 (d), it can be seen that under ultrasound, fecunc@cm conditions, all groups produced green fluorescence. The group with the strongest green fluorescence shift intensity is the group of fecunc@cm combined with hydrogen peroxide and light and heat, and the synergy is also demonstrated.
Example 7
Detection of the photothermal conversion ability of the animal layer surface of hollow fecunc@cm nanomaterial (prepared in example 1): the 4T1 cells are taken as model cells, the BALB/C female mice are taken as model mice, a subcutaneous tumor model of the mice is constructed, and the FeCuNC@CM provided by the invention is adopted as an anti-tumor material. This experiment set 2 groups of experiments a) control, b) FeCuNC@CM material was injected into mice by tail intravenous injection (2.5 mg kg) -1 ). The temperature change at the tumor of the mice was recorded every 30s after 24 hours, wherein the illumination power was 1.0W cm -2 The light recording time was 5min.
From fig. 4 (d), it can be known that the temperature at the tumor of the fecunc@cm group mouse has significantly changed, which illustrates the targeting property and Gao Guangre conversion efficiency of the fecunc@cm nanomaterial. From FIG. 4 (e), it is known that the temperature at the tumor site of FeCuNC@CM group mice can be raised from 34℃to 56℃with a temperature change of about 22 ℃.
Example 8
Detection of antitumor ability of hollow fecunc@cm nanomaterial (prepared in example 1) at animal level: the 4T1 cells are taken as model cells, the BALB/C female mice are taken as model mice, a subcutaneous tumor model of the mice is constructed, and the FeCuNC@CM provided by the invention is adopted as an anti-tumor material. The experiment set up 5 experimental groups (5 mice per group): a) control, b) NC@CM, c) FeNC@CM, d) FeCuNC@CM, e) FeCuNC@CM+near infrared NIR, material was injected into mice by mouse tail intravenous injection (2.5 mg kg) -1 ). Wherein the illumination power is 1.0W cm -2 The illumination time is 5min, and the continuous observation and monitoring are carried out for 18 days. (body weight and tumor volume of mice were recorded every two days during this period)
From fig. 4 (a), no significant change in body weight of mice was seen, indicating no significant toxicity of fecunc@cm; as can be seen from fig. 4 (b) and (c), the tumors of the mice in the control, NC@CM, feNC@CM, feCuNC@CM group were not significantly inhibited, whereas the tumors of the mice in the fecunc@cm+ Near Infrared (NIR) group were significantly reduced after 18 days, and the tumor inhibition rate was higher, indicating that the fecunc@cm+ Near Infrared (NIR) group had excellent antitumor effect.
Claims (11)
1. The FeCuNC nano material is characterized by being a hollow nitrogen-doped carbon nano sphere and having Fe and Cu active sites; the preparation method of the FeCuNC nano material comprises the following steps: adding tetraethyl orthosilicate into the mixed solution of ammonia water and absolute ethyl alcohol or propanol to obtain a template SiO 2 The method comprises the steps of carrying out a first treatment on the surface of the Adding dopamine water solution into the mixed solution, continuously stirring, then adding ferric acetylacetonate, continuously stirring, and then centrifugally washing and drying to obtain Fe-PDA-SiO 2 ；Fe-PDA-SiO 2 Annealing in a protective atmosphere to obtain FeNC; uniformly mixing FeNC, urea and copper phthalocyanine, and then annealing in a protective atmosphere to obtain the FeCuNC nano material.
2. The FeCuNC nanomaterial of claim 1, wherein the FeCuNC nanomaterial has a hydration diameter of 100 to 300nm.
3. The preparation method of the FeCuNC nano material is characterized by comprising the following steps of: adding tetraethyl orthosilicate into the mixed solution of ammonia water and absolute ethyl alcohol or propanol to obtain a template SiO 2 The method comprises the steps of carrying out a first treatment on the surface of the Adding dopamine water solution into the mixed solution, continuously stirring, then adding ferric acetylacetonate, continuously stirring, and then centrifugally washing and drying to obtain Fe-PDA-SiO 2 ；Fe-PDA-SiO 2 Annealing in a protective atmosphere to obtain FeNC; uniformly mixing FeNC, urea and copper phthalocyanine, and then annealing in a protective atmosphere to obtain the FeCuNC nano material.
4. The method for preparing FeCuNC nanomaterial according to claim 3, wherein,
the concentration of ammonia water in the initial solution is 15-35 wt%;
the volume ratio of the ammonia water to the absolute ethyl alcohol or the propanol is 1: 20-1: 40, a step of performing a;
the volume ratio of the tetraethyl orthosilicate to the ammonia water to the absolute ethyl alcohol or the propanol is 1: 15-1: 30;
the concentration of the dopamine solution is 2-5 wt%; the volume ratio of the dopamine solution to the mixed solution is 1:5 to 1:8, 8;
the mass ratio of the ferric acetylacetonate to the dopamine is 1:1.5 to 1:3, a step of;
Fe-PDA-SiO 2 annealing the powder in nitrogen, and heating up at 3-8 ℃ for min -1 The method comprises the steps of carrying out a first treatment on the surface of the The annealing temperature is 700-800 ℃, and the annealing time is 1.5-2.5 h;
fenc, urea and copper phthalocyanine in a mass ratio of 1:40:0.25 to 1:60:0.3;
uniformly mixing FeNC, urea and copper phthalocyanine, annealing in nitrogen, and heating at 2.5-3.5 ℃ for min -1 The method comprises the steps of carrying out a first treatment on the surface of the The annealing temperature is 550-650 ℃, and the annealing time is 1.5-2.5 h.
5. Use of FeCuNC nanomaterial according to claim 1 or 2 for the preparation of a formulation for the decomposition of hydrogen peroxide to generate active oxygen.
6. The use according to claim 5, wherein the FeCuNC nanomaterial is irradiated by near infrared ii light to accelerate the decomposition of hydrogen peroxide and enhance the generation of active oxygen.
7. The method according to claim 6, wherein the illumination power is 0.5-2.2W cm -2 The illumination time is 0.5-10 min, and the concentration of the illumination treatment is 0.5-50 ppm.
8. The use according to claim 6, wherein FeCuNC is mixed with the targeting modifier, stirred and then centrifugally washed to obtain fecunc@cm nanosphere targeting material; the target modifier is an extracted cell membrane, including a cancer cell membrane or a leucocyte membrane; in the mixed system solution, the concentration ratio of FeCuNC to cell membrane is 0.5-2.
9. The use of FeCuNC nanomaterial according to claim 1 or 2 for the preparation of an antitumor drug.
10. The use of FeCuNC nanomaterial according to claim 1 or 2 for the preparation of photo-thermal enhanced antitumor drugs.
11. An antitumor drug comprising FeCuNC nanomaterial as claimed in claim 1 or 2.
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