CN113262301B - Multifunctional anti-tumor nano-drug and preparation method and application thereof - Google Patents
Multifunctional anti-tumor nano-drug and preparation method and application thereof Download PDFInfo
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Abstract
The invention provides a multifunctional anti-tumor nano-drug, which takes the synergistic effect of artemisinin derivatives and sodium nitroprusside as the core content of anti-tumor treatment. The method comprises the steps of taking nanoparticles as carriers, loading or coating a fluorescent/photo-thermal material, an artemisinin derivative and sodium nitroprusside, and coating a thermal phase change material outside the carriers. In the tumor environment, sodium nitroprusside reacts with glutathione excessively expressed in tumor cells to generate nitric oxide gas, so that the gas therapy is realized. When nitric oxide is generated, sodium nitroprusside can also generate a large amount of low-valence iron ions, so that the breaking of the peroxide bridge bond of the artemisinin derivatives is triggered, a large amount of active oxygen is generated, and the tumor cells are effectively killed. The source of the raw materials is wide, the preparation process is simple and easy to operate, and the prepared nanoparticles loaded with the artemisinin derivatives and the sodium nitroprusside have good water solubility, dispersibility and biocompatibility, and are ideal multifunctional cancer treatment reagents.
Description
Technical Field
The invention relates to a multifunctional anti-tumor nano-drug, a preparation method and application thereof, in particular to a near-infrared two-region fluorescence imaging-guided temperature-sensitive response released artemisinin derivative and sodium nitroprusside nano-drug, and application thereof as a photo-thermal and pneumatic therapy reagent, a near-infrared two-region fluorescence and photo-acoustic contrast agent in tumor diagnosis and treatment, belonging to the technical field of biomedicine.
Background
In recent years, with the continuous development of nanotechnology, it is very important to be able to precisely control and synthesize nanomaterials with special optical properties and functions, and low dosage of anticancer drugs, greatly improved therapeutic effect and multiple combination of therapeutic methods are realized through precise control, so that the tolerance of cancer cells to drugs is reversed, and better tumor combination therapy is realized. Artemisinin and its derivatives such as dihydroartemisinin have been attracting much attention because of their anti-tumor activity. In several major studies on the anti-tumor mechanism of artemisinin and its derivatives, it is widely accepted that the ferrous ions contained in heme in vivo activate the peroxide bridge of artemisinin and its derivatives, which breaks down to form ROS to induce apoptosis. Thus, too low an iron content in vivo has prevented the antitumor application of artemisinin and its derivatives. Meanwhile, the artemisinin derivatives have low molecular weight and short blood half-life, and the blood transportation efficiency is low due to intravenous injection. Therefore, for iron-mediated chemotherapy of artemisinin and its derivatives, it is necessary to load artemisinin-like derivatives onto iron-containing carriers.
Diagnosis and treatment integration is to integrate diagnosis modes and treatment methods into a nano platform, and the method is regarded as a novel diagnosis and treatment concept with high safety, specificity and effectiveness. The imaging technology accurately guides the release of the therapeutic drugs, can play an effective monitoring role, and can better predict the therapeutic effect. To date, NIR-II fluorescence imaging has been attracting much attention from researchers as it has excellent imaging effects in light-induced tumor imaging technologies. NIR-II fluorescence imaging, while having so many advantages, may have no way of effectively providing more comprehensive tumor information by just this imaging method. Photoacoustic imaging is an imaging mode created by combining the advantages of optical imaging and ultrasound imaging at the same time, and has deep imaging depth, high sensitivity, and low scattering. Therefore, there is an urgent need to find a comprehensive form of multi-modality imaging means to provide more effective and comprehensive imaging of tumors.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defects of the prior art and providing a multifunctional anti-tumor nano-medicament and a preparation method and application thereof.
The invention provides a multifunctional anti-tumor nano-drug, which comprises porous nano-particles, wherein the porous nano-particles are used as a carrier to load or coat a fluorescent/photothermal material, an artemisinin derivative and sodium nitroprusside, and in order to prevent the drug from leaking prematurely, a thermal phase change material is coated outside the carrier. The invention takes the synergistic effect of artemisinin derivatives and sodium nitroprusside as the core content of anti-tumor treatment. Under the condition of activation of over-expressed glutathione in a tumor microenvironment, a sequential activation response mechanism of gas therapy-chemotherapy is realized, and nitric oxide gas is generated after sodium nitroprusside is activated by over-expressed glutathione in tumor cells, so that gas therapy is realized. Meanwhile, a large amount of low-valence iron ions generated by the sodium nitroprusside can quickly activate artemisinin derivatives to generate a large amount of active oxygen, so that chemotherapy is realized, and the two treatment methods have mutually enhanced synergistic treatment effects.
The invention takes porous nano particles as a carrier, takes near-infrared two-region fluorescent materials as an imaging contrast agent and a photo-thermal reagent, simultaneously loads artemisinin derivatives and sodium nitroprusside, and carries out coating through a phase change material to synthesize the thermosensitive nano medicament. The invention introduces Sodium Nitroprusside (SNP) containing iron, the Sodium Nitroprusside (SNP) is an effective antihypertensive drug and is widely used for treating hypertension emergency in surgical operation and improving cardiac function after infarction, and the SNP exposed to Glutathione (GSH) reduction condition in tumor environment can reduce high-valence iron into low-valence iron, simultaneously generate RSNO, rapidly release Nitric Oxide (NO) and perform related gas treatment. And when GSH is exhausted by SNP, low-valence iron can activate and crack the peroxide bridge bond of the artemisinin derivative to generate a large amount of Reactive Oxygen Species (ROS), so that tumor cells are effectively killed, and chemotherapy is performed. This cascade of qi therapy and chemotherapy, in conjunction with anticancer therapy, produces a therapeutic effect of "1 +1> 2". In conclusion, the artemisinin derivative and the sodium nitroprusside have prominent chemotherapeutic and pneumatic therapy cascade therapeutic effects in tumor treatment.
The technical scheme for further optimizing the invention is as follows:
further, the porous nano carrier particles can be porous silica, polymer nano particles, metal organic framework nano particles, liposome nano particles and other organic and inorganic carriers; the fluorescent/photothermal material can use quantum dots with two-window fluorescence performance, rare earth doped nanoparticles, organic micromolecules, conjugated polymers and the like, and the invention uses silver sulfide quantum dots or organic micromolecule fluorescent dye for further elaboration; the artemisinin derivatives are dihydroartemisinin, artemisinin, artesunate and the like; the phase change material is n-tetradecanol, hydrogel and other temperature sensitive materials.
The invention also provides a preparation method of the multifunctional anti-tumor nano-medicament, which comprises the following steps:
step 1, synthesizing nanoparticles loaded or coated with a fluorescent/photothermal material: selecting a proper porous nano material as a carrier, and loading or coating the fluorescent/photothermal material to obtain nano particles loaded or coated with the fluorescent/photothermal material;
In step 1 of the invention, for the convenience of material preparation, a fluorescent/photothermal material with photothermal action can be selected, and the molar ratio of the porous material to the fluorescent material can be regulated and controlled according to the finally required size of the nanoparticles. And 4, a plurality of thermal phase change materials can be selected in the step 4, such as n-tetradecanol and the like, the molar ratio of the thermal phase change materials to the nanoparticles is regulated according to the required shell thickness, and the thermal phase change materials are washed by a centrifugal machine at the rotating speed of 7000-10000 rpm.
In the step 2, 1-5 mg of the nanoparticles obtained in the step 1 are dispersed in 1-6 mL of absolute ethanol, then 1-200 mg of artemisinin derivatives are added, the mixture is stirred at room temperature for 1-16 h, and a material is washed by using an ethanol solution (a mixed solution of ethanol and deionized water, v/v =3: 1) with the mass concentration of 30% -60%, so that the nanoparticles loaded with the artemisinin derivatives are obtained.
In the step 3, the nanoparticles obtained in the step 2 are dissolved in 1-5 mL of deionized water, 1-200 mg of sodium nitroprusside is added, and the mixture is stirred at room temperature in a dark place for 1-16 hours to obtain sodium nitroprusside-loaded nanoparticles. Since sodium nitroprusside is easily decomposed by light, the load process needs to be processed under the condition of keeping out of the sun.
In the step 1, the fluorescent/photothermal material is selected to be a fluorescent/photothermal material having a photothermal effect, and when the fluorescent/photothermal material is an inorganic material, a coating manner is selected, and when the fluorescent/photothermal material is an organic material, a loading manner is selected.
The invention complements the advantages and the disadvantages by fluorescence imaging and photoacoustic imaging to form a bimodal imaging guided tumor treatment mode, compensates the limitation caused by a single imaging means, and improves the biomedical diagnosis capability.
In the step 2, the optimal molar ratio of the nanoparticles to the artemisinin derivatives is 1: 2; stirring at room temperature until ethanol is completely volatilized, then washing by using a centrifugal machine, and carrying out centrifugal washing by using the centrifugal machine during washing, wherein the rotating speed is 7000-10000 rpm.
In the step 3, the optimal molar ratio of the nanoparticles to the sodium nitroprusside is 1: 1; and after the reaction is finished, the deionized water is used for centrifuging and washing the material for 3 times or more, and the rotating speed of a centrifugal machine is 7000-10000 rpm.
The nano-drug provided by the invention is used in chemotherapy-qi therapy anti-tumor combination therapy.
In the invention, artemisinin derivatives and sodium nitroprusside are loaded in a carrier, and in a tumor environment, the sodium nitroprusside reacts with glutathione excessively expressed in tumor cells to generate nitric oxide gas, thereby realizing gas treatment; when nitric oxide is generated, sodium nitroprusside can also generate a large amount of low-valence iron ions, so that artemisinin derivatives are quickly activated, peroxide bridge bonds of the artemisinin derivatives are broken, a large amount of active oxygen free radicals are generated, tumor cells are effectively killed, and chemotherapy is realized. The two treatments have synergistic therapeutic effects which are mutually enhanced. In a word, the invention realizes the sequential activation response mechanism of the chemotherapy-chemotherapy by using the condition of glutathione activation over-expressed in a tumor microenvironment, provides an anti-tumor combined treatment method of the chemotherapy-chemotherapy by combining artemisinin derivatives and sodium nitroprusside anti-cancer drugs, and provides a new idea for the research and development of tumor drugs.
Furthermore, the nano-drug releases artemisinin derivatives and sodium nitroprusside through photothermal response to realize anti-tumor combined treatment and near-infrared two-region fluorescence/photoacoustic multi-modal imaging-guided photothermal/chemotherapy/qi therapy application.
After entering the tumor, the medicine of the invention generates fluorescence/photoacoustic imaging and photothermal action by near infrared laser irradiation, so that the phase-change material is melted, the artemisinin derivative and sodium nitroprusside are released, and further chemotherapy and qi therapy combined treatment is initiated. The nano-drug can be used for multi-modal imaging-guided tumor-targeted photothermal/chemotherapy/qi therapy collaborative diagnosis and treatment.
Compared with the prior art, the technical scheme adopted by the invention has the following technical effects: selecting nanoparticles with a loading effect as a carrier, and loading artemisinin derivatives and sodium nitroprusside in the carrier. The source of the raw materials is wide, the preparation process is simple and easy to operate, and the prepared nanoparticles loaded with the artemisinin derivatives and the sodium nitroprusside have good water solubility, dispersibility and biocompatibility, and are ideal multifunctional cancer treatment reagents.
Drawings
FIG. 1 is a schematic diagram of the anti-cancer mechanism of artemisinin derivatives and sodium nitroprusside in example 1 of the present invention.
FIG. 2 is a high-resolution transmission electron microscope image of AS nanoparticles in example 1 of the present invention.
FIG. 3 shows the concentration of the product in example 3 of the present invention at 808 nm, 1W/cm2Photo-thermal temperature rise curve under near-infrared light irradiation.
FIG. 4a is a graph showing the release of dihydroartemisinin under laser irradiation in example 3 of the present invention; FIG. 4b is a graph showing the release of sodium nitroprusside under laser irradiation in example 3 of the present invention.
FIG. 5a is a graph showing the in vitro fluorescence as a function of concentration for the product of example 3 of the present invention; fig. 5b is a graph of the intensity of photoacoustic signal as a function of concentration for the product in example 3 of the present invention.
FIG. 6 is a schematic representation of NO production following GSH addition to the product of example 3 of the present invention.
Detailed Description
The technical scheme of the invention is further explained in detail by combining the drawings as follows: the present embodiment is implemented on the premise of the technical solution of the present invention, and a detailed implementation manner and a specific operation process are given, but the protection authority of the present invention is not limited to the following embodiments.
Example 1 preparation of amino-modified mesoporous Ag2S@SiO2Core-shell nanoparticles
Using silicon dioxide (SiO)2) As the carrier particles, silver sulfide quantum dots (Ag) were used2S QDs) as a near-infrared two-zone fluorescent reagent and a photothermal reagent, with n-tetradecanol as a phase change material. As shown in FIGS. 1 and 2, the following is mesoporous Ag modified with amino group2S@SiO2The specific preparation method of the core-shell nano-particles comprises the following steps: synthesis of Ag by conventional method using thermal decomposition method2S QDs, thiol-terminated quantum dots were dispersed with chloroform and stored in a 4 ℃ refrigerator for future use. 0.05 g CTAB (cetyltriethylammonium bromide) was dissolved in 2.5 mL of deionized water, followed by addition of 0.25 mL of Ag dispersed in chloroform2In the S QDs, vigorously stirring for 30 min to form a brown yellow sol; stirring the sol in a 60 deg.C water bath for 10 min to evaporate chloroform; then adding 22.5 mL of deionized water and 0.6 mL of ammonia water, adding 0.2 mL of TEOS (tetraethylorthosilicate), 50 muL of APTES (3-aminopropyltriethoxysilane) and 1.5 mL of ethyl acetate after the temperature rises to 70 ℃, reacting for 3 hours, and washing with ethanol for three times (washing by using a centrifuge at the rotating speed of 7000-10000 rpm); removing CTAB template, namely using 6 mg/mL solution prepared from ammonium nitrate and ethanol, refluxing for 2 hours at 60 ℃, and removing for three times to obtain the mesoporous Ag with amino modification on the surface2S@SiO2Core-shell nanoparticles (AS NPs, i.e., AS nanoparticles).
Example 2 preparation of multifunctional antitumor Nanomedicines
Step 1, amino-modified mesoporous Ag2S@SiO2Core-shell nanoparticle formation reference was made to example 1.
Example 3 application of multifunctional antitumor Nanometric drugs
Example 2 preparation of multifunctional Ag2S@SiO2The DHA/SNP/TD diagnosis and treatment probe can be used for photothermal/chemotherapy/gas treatment of tumors under near infrared light irradiation on one hand, and can be used for near infrared two-region fluorescence and photoacoustic imaging on the other hand.
The effect of the artemisinin derivative/sodium nitroprusside combination therapy was evaluated experimentally as follows.
Photo-thermal property detection
Evaluating photothermal effect, performing photothermal effect test with solutions of AS NPs of different concentrations, and subjecting the AS NPs solutions to 808 nm laser at 1W/cm2Irradiation was carried out for 10 minutes under the conditions. AS shown in fig. 3, the photothermal effect of the AS NPs was significantly dependent on the concentration, and the temperature did not change significantly within 10 min in the absence of AS, while the photothermal effect of 70 ℃ was achieved in the presence of AS. In summary, these experiments show that the AS NPs material has good photo-thermal effect in nature, and provides a simple method for simultaneously realizing the dissolution of PTT and heat-sensitive 1-TD and the release of the drug.
Thermosensitive release of di-and n-tetradecanol
The artemisinin derivative and sodium nitroprusside which are not irradiated with light are released very slowly, the release rates are respectively 19% -17%, and after the light is applied, the release rates reach 63% and 54%, respectively, as shown in fig. 4a and 4 b. Furthermore, in view of the reversible phase transition characteristics of 1-TD, multiple NIR laser irradiation on/off processes were performed to achieve "on-demand" drug release behavior. For the light experiments, five cycles were performed. It can be observed from the data that the drug release rate increases dramatically when the laser is turned on and drops dramatically upon turning off the laser.
Three, near infrared two-zone fluorescence imaging
Respectively preparing AS-DHA/SNP/TD-FA aqueous solutions with different concentrations, and detecting the fluorescence signals of the solutions by using a living body fluorescence imager, wherein AS NPs show concentration-dependent fluorescence signals in the aqueous solutions under 808 nm laser radiation AS shown in figure 5 a. The nano probe is shown to have good near-infrared two-region fluorescence imaging effect.
Four, photoacoustic imaging
Respectively preparing different Ag2200 mu L of AS-DHA/SNP/TD-FA aqueous solution with S concentration is put in a small test tube, and then the photoacoustic signal is detected by a photoacoustic imager, AS shown in figure 5b, along with Ag in the nano diagnosis and treatment probe2And the photoacoustic signal of the nano probe is gradually enhanced due to the increase of the S concentration, which shows that the nano probe has a good photoacoustic imaging effect.
In addition, Ag prepared in example 22S@SiO2And (3) adding GSH into DHA/SNP/TD to detect the release amount of NO, specifically as shown in figure 6, finding that sodium nitroprusside can reduce high-valence iron into low-valence iron under the GSH reduction condition by the diagnosis and treatment probe, simultaneously generate RSNO and quickly release NO.
The above description is only an embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can understand that the modifications or substitutions within the technical scope of the present invention are included in the scope of the present invention, and therefore, the scope of the present invention should be subject to the protection scope of the claims.
Claims (9)
1. A multifunctional anti-tumor nano-drug is characterized in that: the fluorescent/photothermal material, the artemisinin derivative and sodium nitroprusside are loaded or coated by taking the organic/inorganic nano particles as a carrier, and the thermal phase change material is coated outside the carrier; the nanoparticles are porous silica; the fluorescent/photothermal material is silver sulfide quantum dots; the artemisinin derivatives are dihydroartemisinin, artemisinin or artesunate; the thermal phase change material is n-tetradecanol.
2. The method for preparing the multifunctional anti-tumor nano-drug according to claim 1, comprising the following steps:
step 1, synthesizing nanoparticles loaded or coated with a fluorescent/photothermal material: selecting a proper porous nano material as a carrier, and loading or coating the fluorescent/photothermal material to obtain nano particles loaded or coated with the fluorescent/photothermal material;
step 2, preparing the nanoparticles loaded with the artemisinin derivatives: dispersing the nanoparticles obtained in the step (1) in absolute ethyl alcohol, adding artemisinin derivatives, uniformly stirring, and washing to obtain nanoparticles loaded with a fluorescent/photo-thermal material and the artemisinin derivatives;
step 3, preparing the nanoparticles loaded with the artemisinin derivatives and sodium nitroprusside: dissolving the nanoparticles obtained in the step (2) in deionized water, adding sodium nitroprusside, and uniformly stirring to obtain nanoparticles loaded with the fluorescent/photothermal material, the artemisinin derivatives and the sodium nitroprusside;
step 4, preparing the nanoparticles coated by the thermal phase-change material: and (4) selecting a proper thermal phase change material, and loading the thermal phase change material on the surface or in the pores of the nanoparticles obtained in the step (3) to control the release of the drug.
3. The preparation method of the multifunctional anti-tumor nano-drug according to claim 2, wherein in the step 2, 1-5 mg of the nano-particles obtained in the step 1 are dispersed in 1-6 mL of absolute ethanol, 1-200 mg of artemisinin derivatives are added, the mixture is stirred at room temperature for 1-16 h, and the material is washed by using an ethanol solution with a mass concentration of 30-60% to obtain the nano-particles loaded with the artemisinin derivatives.
4. The preparation method of the multifunctional anti-tumor nano-drug according to claim 3, wherein in the step 3, the nano-particles obtained in the step 2 are dissolved in 1-5 mL of deionized water, 1-200 mg of sodium nitroprusside is added, and the mixture is stirred at room temperature in the dark for 1-16 h to obtain the sodium nitroprusside-loaded nano-particles.
5. The method for preparing a multifunctional anti-tumor nano-drug according to claim 3, wherein in the step 1, the fluorescent/photothermal material is selected to be a fluorescent/photothermal material having photothermal effect, and when the fluorescent/photothermal material is an inorganic material, a coating manner is selected.
6. The method for preparing the multifunctional anti-tumor nano-drug according to claim 3, wherein in the step 2, the optimal molar ratio of the nanoparticles to the artemisinin derivative is 1: 2; and (3) carrying out centrifugal washing by using a centrifugal machine during washing, wherein the rotating speed is 7000-10000 rpm.
7. The method for preparing the multifunctional anti-tumor nano-drug according to claim 3, wherein in the step 3, the optimal molar ratio of the nanoparticles to the sodium nitroprusside is 1: 1; and (4) after the reaction is finished, using deionized water to centrifugally wash the material, wherein the rotating speed of the centrifugal machine is 7000-10000 rpm.
8. Use of the multifunctional anti-tumor nano-drug of any one of claims 1 to 7 in the preparation of a chemotherapeutic-pneumatic therapy anti-tumor combination therapy drug.
9. The medical application of the multifunctional anti-tumor nano-drug according to claim 8, wherein the nano-drug releases artemisinin derivatives and sodium nitroprusside through photo-thermal response to realize anti-tumor combination therapy and near-infrared two-region fluorescence/photo-acoustic multi-modal imaging-guided photo-thermal/chemotherapy/gas therapy application.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103948585A (en) * | 2014-04-17 | 2014-07-30 | 中山大学中山眼科中心 | Application of artemisinin in preparing medicament for preventing and treating neurological diseases |
| CN103961712A (en) * | 2014-05-02 | 2014-08-06 | 中国科学技术大学 | Superparamagnetic ferroferric oxide nano particle drug carrier, preparation method and application thereof |
| CN105797157A (en) * | 2016-04-26 | 2016-07-27 | 中国科学技术大学 | Preparation method and application of porous core-shell double-metal organic framework nano drug carrier |
| CN108785673A (en) * | 2018-07-06 | 2018-11-13 | 重庆医科大学 | A kind of Prussian blue similar object nanometer photo-thermal therapy agent of load medicine and preparation method thereof that sodium nitroprussiate is conjugated |
| CN110101857A (en) * | 2019-04-22 | 2019-08-09 | 北京化工大学 | A kind of copper-based photo-thermal controlled-release nanoparticle and preparation method |
-
2021
- 2021-05-18 CN CN202110539011.7A patent/CN113262301B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103948585A (en) * | 2014-04-17 | 2014-07-30 | 中山大学中山眼科中心 | Application of artemisinin in preparing medicament for preventing and treating neurological diseases |
| CN103961712A (en) * | 2014-05-02 | 2014-08-06 | 中国科学技术大学 | Superparamagnetic ferroferric oxide nano particle drug carrier, preparation method and application thereof |
| CN105797157A (en) * | 2016-04-26 | 2016-07-27 | 中国科学技术大学 | Preparation method and application of porous core-shell double-metal organic framework nano drug carrier |
| CN108785673A (en) * | 2018-07-06 | 2018-11-13 | 重庆医科大学 | A kind of Prussian blue similar object nanometer photo-thermal therapy agent of load medicine and preparation method thereof that sodium nitroprussiate is conjugated |
| CN110101857A (en) * | 2019-04-22 | 2019-08-09 | 北京化工大学 | A kind of copper-based photo-thermal controlled-release nanoparticle and preparation method |
Non-Patent Citations (3)
| Title |
|---|
| An Intelligent and Tumor-Responsive Fe2+ Donor and Fe2+-Dependent Drugs Cotransport System;Huijuan Zhang等;《ACS Appl. Mater. Interfaces》;20161118;第33484-33498页 * |
| Controllable synthesis of dual-MOFs nanostructures for pH-responsive artemisinin delivery, magnetic resonance and optical dual-model imaging-guided chemo/photothermal combinational cancer therapy;Dongdong Wang等;《Biomaterials》;20160524;第27-40页 * |
| Gold Nanorods Coated with Mesoporous Silica Shell as Drug Delivery System for Remote Near Infrared Light-Activated Release and Potential Phototherapy;Ji Liu等;《small》;20151231;第2323-2332页 * |
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