CN111374960A - EGFR receptor targeted tumor diagnosis and treatment radioactive nanoparticle and preparation method thereof - Google Patents
EGFR receptor targeted tumor diagnosis and treatment radioactive nanoparticle and preparation method thereof Download PDFInfo
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Abstract
The invention relates to an EGFR receptor targeted radioactive nanoparticle and a preparation method thereof, and the composition comprises 5-10nm iron oxide nanoparticles, polyacrylic acid, cisplatin, dopamine, and GE11 small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH-I-K-H-Y-G-Y-P-Q-N-V-I-K) containing tyrosine-histidine-tryptophan-tyrosine-glycine-tyrosine-threonine-proline-glutamine-asparagine-valine-isoleucine-lysine-azidoacetic acid2)m‑N3) Containing copper-64: (64Cu) radionuclide. Compared with the prior art, the prepared nano-particles can be used for radiotherapy-chemotherapy combination treatment guided by PET/MRI/PAI imaging diagnosis.
Description
Technical Field
The invention relates to a novel nanoparticle and a preparation method thereof, in particular to a tumor EGFR receptor targeted cisplatin-carried radionuclide-labeled nanoparticle and a preparation method thereof.
Background
The morbidity and mortality of tumors are increased year by year, and people are always actively exploring how to realize radical treatment of tumors. The single treatment methods such as chemotherapy, radiotherapy, photothermal therapy, immunotherapy and the like have limitations, so the treatment effect is still not ideal. With the development of nanotechnology, various therapeutic strategies have been integrated into a single platform based on nanocarriers, which has proven to be effective.
However, chemotherapy in combination with radiotherapy is still the most common strategy for tumor treatment. Chemotherapy achieves therapeutic goals by killing cancer cells using chemotherapeutic drugs. Chemotherapy is one of the most effective means for treating cancer at present, and is a means for systemic treatment, and no matter what way of administration (oral administration, intravenous administration, body cavity administration and the like) is adopted, chemotherapy drugs are distributed throughout most organs and tissues of the whole body along with blood circulation. Therefore, chemotherapy is the main treatment for some tumors prone to systemic dissemination and for tumors in the middle and late stages that have metastasized.
Radiation therapy is a local treatment for tumors using radiation. The efficacy of radiation therapy depends on the radiation sensitivity, which is directly influenced by the oxygen content of the tumor cells, e.g. small volume of early stage tumor, good blood circulation, good efficacy with few hypoxic cells, large volume of late stage tumor, poor blood circulation in tumor, even necrosis in the center, and low radiation sensitivity.
Cisplatin has the characteristics of wide anticancer spectrum, strong action, synergistic action with various antitumor drugs, no cross drug resistance and the like, and is one of the most commonly used drugs in the current combined chemotherapy. Meanwhile, because platinum element in cisplatin has high atomic number, cisplatin is also a very effective drug for tumor radiotherapy sensitization. Therefore, by using the cisplatin to carry out the combined treatment of the tumor radiotherapy and the tumor chemotherapy, the synergistic effect between the chemotherapy and the radiotherapy can be realized, and the dosage of the medicine and the radioactive dose can be reduced. However, cisplatin is non-specific to tumors and has the problem of dose tolerance in normal tissues, regardless of chemotherapy or radiotherapy. Therefore, the realization of the specific targeting of the drug tumor is an effective way to reduce the treatment dosage, protect the normal tissues to the maximum extent and further realize the maximum curative effect.
EGFR receptors are highly expressed on malignant cells of various epithelial origins, including lung cancer, brain glioma, colorectal cancer, breast cancer and the like. Wherein the GE11 small peptide with the sequence of Y-H-W-Y-G-Y-T-P-Q-N-V-I-K can specifically target EGFR receptor. Research shows that the nano-carrier coupled with the GE11 small peptide can realize the specific and high-efficiency enrichment of positive tumors of EGFR receptors.
However, when drug-loaded nanocarriers are able to achieve the maximum tumor accumulation to begin radiotherapy, image guidance is required.
PET is the only novel imaging technology which can display the biomolecular metabolism, receptor and nerve medium activity on a living body at present, and has the advantages of high sensitivity, whole-body imaging and good safety.
Magnetic resonance imaging has excellent resolution for soft tissue. Because of the extremely fine spatial resolution and the excellent tissue resolution, the MRI can display the anatomical structure of the tissue with high resolution and simultaneously carry out fine and accurate positioning and quantitative analysis on the molecular imaging characteristics of the deep tissue. Since MRI does not use X-rays harmful to the human body and contrast agents which easily cause allergic reactions, it is not harmful to the human body. The method has great value in diagnosing diseases of all systems of the whole body, especially early tumors.
Photoacoustic imaging is a new biomedical imaging method developed in recent years, both non-invasive and non-ionizing. The photoacoustic signal generated by the biological tissue carries the light absorption characteristic information of the tissue, and the light absorption distribution image in the tissue can be reconstructed by detecting the photoacoustic signal. The photoacoustic imaging combines the advantages of high selectivity in pure optical tissue imaging and deep penetration in pure ultrasonic tissue imaging, can obtain a tissue image with high resolution and high contrast, and can realize deep in-vivo tissue imaging of 50 mm.
In chinese patent CN 102539760 a, a folic acid ligand modified iron oxide nanoparticle having an in vitro tumor targeting effect and a folic acid ligand modified iron oxide nanoparticle having an in vitro tumor targeting effect are invented, wherein the iron oxide nanoparticle uses iron oxide as an inner core, and the surface of the iron oxide nanoparticle is covalently modified with folic acid. Glucan active agent particles are adsorbed on the surfaces of the iron oxide nanoparticles, and the iron oxide nanoparticles are folic acid-glucan-iron oxide nanoparticles. CN 104984371A discloses a tumor-targeted radioactive nanoparticle, wherein a carrier of the tumor-targeted radioactive nanoparticle is an iron oxide nanoparticle (the diameter is less than or equal to 10nm), surface modification molecules are polyacrylic acid and alkynylamine compounds, and a radionuclide is fluorine-18. Although they have stronger tumor targeting, the success rate of early diagnosis of tumors can be effectively improved. However, the PET/MRI/PAI fusion technology can not be realized to guide the combined treatment of tumor radiotherapy and chemotherapy.
Disclosure of Invention
The present invention aims to overcome the defects of the prior art and provide a tumor EGFR receptor targeted radioactive nanoparticle, which comprises a carrier, a drug, a surface modification molecule, a tumor targeting molecule and a radionuclide.
The purpose of the invention can be realized by the following technical scheme: a tumor EGFR receptor-targeted radioactive nanoparticle, characterized by:
the nanoparticles comprise a carrier, a drug, a surface modification molecule, a tumor targeting molecule and a radionuclide, wherein the mass ratio of the carrier, the drug, the surface modification molecule and the tumor targeting molecule is 1-2: 0.2-0.8: 1-2: 0.1-0.5, and the dosage of the radionuclide is 56MBq/m3；
The carrier is iron oxide nano-particles, and the diameter of the iron oxide nano-particles is 5-10 nm;
the drug is cisplatin, is a broad-spectrum antitumor drug, and has a chemical formula of [ Pt (NH)2)]Cl2；
The surface modification molecules are one or more of polyacrylic acid, dopamine and PEG;
the tumor EGFR targeting molecule is a small peptide containing tyrosine-histidine-tryptophan-tyrosine-glycine-tyrosine-threonine-proline-glutamine-asparagine-valine-isoleucine-lysine-azidoacetic acid;
the radionuclide is copper-64.
The iron oxide nanoparticles are iron oxide nanoparticles, ferroferric oxide nanoparticles or a mixture of the two.
The molecular weight of the polyacrylic acid is 1000-5000Da, and the molecular formula of the dopamine is C8H11NO2The PEG is PEG (NH) with one end being amino and the other end being alkynyl modified2PEG-Alkyne) with a molecular weight of 1000-.
The chemical formula of the small peptide containing tyrosine-histidine-tryptophan-tyrosine-glycine-tyrosine-threonine-proline-glutamine-asparagine-valine-isoleucine-lysine-azidoacetic acid is Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3Wherein m is 2-9.
The preparation method of the tumor EGFR receptor targeted radioactive nanoparticle is characterized by comprising the following steps:
(1) preparation of the support
The iron oxide nanoparticles are prepared by reacting ferric chloride, polyacrylic acid and diethylene glycol to obtain iron oxide nanoparticles;
(2) cisplatin Loading
The cisplatin loading method comprises the steps of activating cisplatin by silver nitrate to obtain hydrated cisplatin, and then adding the hydrated cisplatin into the iron oxide nanoparticles for reaction to obtain the cisplatin-loaded iron oxide nanoparticles;
(3) dopamine coating
Dispersing the cisplatin-carried iron oxide nanoparticles prepared in the step (2) into dopamine aqueous solution with the pH value of 8.4, coating for 2-30 minutes, and then performing ultrafiltration to obtain dopamine-coated cisplatin-carried iron oxide nanoparticles;
(4) PEG modification
Reacting NH2Adding a PEG-Alkyne solution into the solution containing the iron oxide nanoparticles prepared in the step (3), and performing ultrafiltration after reaction to obtain PEG modified, dopamine coated and cisplatin loaded iron oxideA nanoparticle;
(5) small peptide coupling
Mixing the iron oxide nanoparticles prepared in the step (4) with EGFR receptor targeting small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) Coupling to obtain small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles, wherein m is 2-9;
(6)64cu nuclide labeling
Mixing the iron oxide nanoparticles prepared in the step (5) with64Cu reacts via the catechol group on dopamine with64In CuCl64Cu chelating reaction to obtain64Cu-labeled, 11 small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles represented by GE11-64CuPt-PDA@FeyOxI.e. the lung cancer targeted radioactive nanoparticles.
The pH of all steps was adjusted with Tris-Tricine buffer at pH 8.5.
In the step (1), ferric chloride, polyacrylic acid (PAA) and diethylene glycol (DEG) are used, NaOH solution dissolved in DEG is rapidly added at the temperature of 180-240 ℃, the reaction is carried out for 5-15min, and the iron oxide nanoparticles are prepared after cooling, wherein the molar ratio of the ferric chloride to the PAA is 1 (1-3), and the mass volume ratio of the ferric chloride to the DEG is 1:45-55 mol/L.
The silver nitrate activated cisplatin in the step (2) is prepared by mixing silver nitrate and cisplatin according to a molar ratio of 1-5: 1, and reacting at 40-60 ℃ to obtain hydrated cisplatin; the cis-platinum hydrate and the iron oxide nanoparticles are mixed according to the mass ratio of 3: 3-6, and are stirred and reacted for 0.5-2 hours through magnetic stirring to obtain the cis-platinum-loaded iron oxide nanoparticles.
In the step (3), the mass ratio of the cisplatin-carried iron oxide nanoparticles to the dopamine is 3-8: 1; the concentration range of the cisplatin-carried iron oxide nanoparticles in the dopamine aqueous solution is 10-100 mg/L;
the solution containing the iron oxide nanoparticles prepared in the step (3) in the step (4) is prepared by adding the iron oxide nanoparticles into a Tris-HCl solution, NH2The PEG-Alkyne solution is prepared by reacting NH2-PEG-Alkyne in ultrapure water and then mixing the two, NH2The mass ratio of the PEG-Alkyne to the iron oxide nanoparticles is 2: 2-4.
CuSO is also added in the coupling reaction in the step (5)4Mixing the solution and NaVc solution with the PEG-modified, dopamine-coated and cisplatin-loaded iron oxide nanoparticles and small peptides prepared in the step 4), and stirring and reacting at 30-60 ℃ for 0.1-1 h; the CuSO4The concentration is 20-40mmol/mL, and the concentration of NaVc in the NaVc solution is 60-120 mmol/mL; the PEG-modified dopamine-coated cisplatin-loaded iron oxide nanoparticles, small peptides and CuSO4The mass ratio of NaVc to NaVc is 1.5:0.2:0.1: 0.24;
the chelating reaction in the step (6) has the reaction temperature of 30-45 ℃ and the reaction time of 0.1-1 h.
Compared with the prior art, the invention mainly comprises iron oxide nanoparticles used as a carrier and an MRI contrast agent, a chemotherapy and radiotherapy sensitizing drug cisplatin, dopamine with photothermal effect and a tumor EGFR receptor targeting molecule GE11 small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) And radionuclide copper-64:
(1) carrier and MRI contrast agent-iron oxide nanoparticles
The size of the iron oxide nano material is between 5 and 10nm, the magnetic resonance imaging nano material has good biocompatibility and good magnetic resonance T1/T2 imaging effect, and is widely applied to biomedical application.
(2) Chemotherapy and radiotherapy sensitizing drug cisplatin
Cisplatin is a broad-spectrum anticancer drug, is combined with DNA to cause cross-linking, thereby destroying the function of the DNA and inhibiting cell mitosis, and can show curative effect when being clinically used for various solid tumors such as ovarian cancer, lung cancer and the like; and cisplatin is a high-efficiency radiotherapy sensitizer, can effectively improve the radiotherapy effect, and realizes radiotherapy and chemotherapy combined treatment by a simple method.
(3) Dopamine with photothermal effect
Dopamine is a very important neurotransmitter and is a small molecule mimetic of mussel adhesive protein, which can self-polymerize on the surface of many materials and shows good biocompatibility. The polydopamine has strong near infrared absorption and high photothermal conversion efficiency, and can be used for photothermal therapy and photoacoustic imaging.
(4) Targeting molecule GE11(Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3)
The aggregation of particles at the tumor site can seriously affect the imaging diagnosis and treatment effect of the tumor. Studies have shown that there is high or abnormal expression of EGFR in many solid tumors, EGFR being a receptor for Epithelial Growth Factor (EGF) cell proliferation and signaling, one of the non-small cell lung cancer marker biomolecules. Therefore, a series of antibodies or inhibitors have been developed in recent years for targeted therapy of non-small cell lung cancer against the EGFR receptor. Meanwhile, small peptides specifically targeting EGFR receptors, such as small peptides containing Y-H-W-Y-G-Y-T-P-Q-N-V-I-K sequences, are also currently screened by phage display technology and computer aided design technology. The small peptide can target EGFR receptor for tumor detection and drug-loading treatment. Therefore, the patent designs a targeting probe with an EGFR receptor, improves the aggregation of the probe at a tumor part, and finally improves the imaging diagnosis and treatment effects.
(5) Radionuclide-copper-64
Copper-64 is a novel nuclide with a long half-life that can be coupled to a variety of compounds, and it produces β-The particles can be used for radiotherapy of tumors, serve as nuclides for PET contrast, and are easy to obtain images with high resolution.
Constructing a marker which loads cis-platinum, is coated with dopamine on the surface64Cu nuclide and coupling GE11(Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) The nano-probe of the small peptide can specifically target EGFR positive tumor, and based on the EGFR positive tumor, the radiotherapy-chemical drug therapy combination treatment guided by the positron emission computed tomography, the magnetic resonance imaging and the photoacoustic imaging diagnosis of the tumor tissue is realized.
The tumor EGFR receptor targeting radioactive nanoparticles prepared by the invention are mainly used for PET/MRI/PAI multi-mode guided radiotherapy-chemotherapy combined treatment of EGFR positive tumors, and realize diagnosis and treatment integration.
The positive progress effects of the invention patent are as follows:
(1) the superparamagnetic iron oxide nanoparticle has good biocompatibility, can be used as a contrast agent for MRI imaging, and can be used as a carrier for a series of modifications. Therefore, the invention can simultaneously carry out PET, PAI and MRI, improve the diagnostic sensitivity, accurately position the focus position and guide radiotherapy-chemotherapy combined treatment, and has obvious treatment effect. This is not available with conventional contrast agents.
(2) The surface of the prepared iron oxide nano particle is coated by polyacrylic acid and contains a large number of carboxyl groups, and through complexation, the efficient loading on the surface of the cis-platinum nano particle can be realized, and the cis-platinum has a radiotherapy sensitization effect and can efficiently realize radiotherapy-chemotherapy combination treatment.
(3) The dopamine coating can effectively reduce the release of cisplatin in vivo circulation before reaching tumor parts, cause normal human body injury, improve the biocompatibility of the particles and realize the effect64No carrier labeling of Cu, direct coupling of PEG molecules. Meanwhile, due to good photo-thermal effect, photo-thermal treatment and photo-acoustic imaging can be carried out after coating.
(4) The coupled GE11 small peptide has high specificity to EGFR receptor, improves the aggregation of particles at tumor sites, and finally improves the imaging diagnosis and treatment effect.
(5)64Cu is a long half-life positive electron nuclide and is utilized64Cuβ+The 511keV photons produced by the decay can be PET imaged.
(6) The iron oxide nanoparticles can release free iron which can trigger endogenous H of the tumor2O2Decompose, effectively relieve tumor hypoxia environment, and improve therapeutic effect.
Drawings
Figure 1 is a schematic representation of tumor EGFR receptor targeted radioactive nanoparticles.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments.
As shown in the figure1, the tumor EGFR receptor targeted radioactive nanoparticle comprises iron oxide nanoparticles, polyacrylic acid, cisplatin, dopamine, GE11 small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) And64and (3) Cu. The respective uses of these components are that iron oxide nanoparticles are used as a carrier, simultaneously for MRI; polyacrylic acid is used as a surface modification molecule of the iron oxide nanoparticles, so that the nano particles are stabilized, and cis-platinum can be carried; cisplatin is used as chemotherapeutic medicine and radiotherapy sensitizer; dopamine is used as a coating layer; GE11 small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) Is a targeting molecule, targeting the EGFR receptor;64cu is a radionuclide for PET imaging.
Example 1
The preparation method of the tumor diagnosis and treatment radioactive nanoparticle targeting the tumor EGFR receptor comprises the following steps:
taking 8mmol PAA and 4mmol FeCl3Dissolved in diethylene glycol DEG (30mL), and the mixture was transferred to a 50mL three-necked flask and placed under vigorous stirring in a microwave oven. When the temperature reached 220 deg.C, the prepared 2mL NaOH solution (100mg/mL, 80 deg.C) in DEG was added quickly. Further heating and mixing for 10min by using microwave heating power of 800W, and cooling to room temperature of 20 ℃ to obtain black ferric oxide colloid. Obtaining the final product after centrifugal washing.
Taking 16.9mg AgNO3Dissolving in 1mL of water, dissolving 15mg of cisplatin in 1mL of water, and mixing the obtained solution with AgNO3The solution is dropwise added into cisplatin, heated at 50 ℃ for reaction for 1h, and then centrifuged at 6000r/min for 5min to separate AgCl.
And (2) putting 1.5mg of iron oxide nanoparticle suspension into a glass reaction bottle, adding 1mL of Tris-Tricine buffer solution, adding 0.6mg of hydrated cis-platinum, slowly stirring at room temperature for reaction for 1 hour, and dialyzing to separate redundant cis-platinum.
Weighing 0.3mg of dopamine, dissolving in 1mL of Tris-Tricine buffer solution, slowly adding into the cisplatin-loaded reaction solution, reacting for 0.5h, centrifuging at 6000r/min for 5min to separate redundant dopamine, adding Tris-Tricine buffer solution, and centrifuging and cleaning for three times.
Weighing 1.5mg of PEG, adding the PEG into the reaction solution, reacting for 12h, then centrifuging at 6000r/min for 5min for separation, adding Tris-Tricine buffer solution for centrifuging and washing for three times, and keeping the volume of the PEG to be 1 mL.
Weighing CuSO410mg, 1mL of water was added to make CuSO4A solution; weighing NaVc 12mg, and adding 0.5mL of water to prepare a NaVc solution; to a reaction flask containing 1mL of the above suspension was added 150. mu.g of GE11 small peptide, followed by 10. mu.L of CuSO4And (3) mixing the solution with 10 mu L of NaVc solution, placing the reaction bottle in a water bath at 50 ℃ for slowly stirring, reacting for 0.5h, and centrifuging at 6000r/min for 5min to separate the magnetic nanoparticles from unreacted GE11 and other impurities.
Mixing 10. mu.L (81.4MBq)64CuCl2Adding into the above reaction solution, shaking, reacting at room temperature for 0.5h, centrifuging at 6000r/min for 5min, and separating to obtain the final product64Cu labeling, GE11 small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles, namely the tumor EGFR receptor targeted radioactive nanoparticles.
Example 2
A tumor EGFR receptor targeted radioactive nanoparticle is prepared by the following method:
(1) preparation of the support
Adding ferric chloride, polyacrylic acid (PAA) and diethylene glycol (DEG) into NaOH solution dissolved in DEG rapidly at 180 ℃, reacting for 15min, and cooling to obtain iron oxide nanoparticles, wherein the molar ratio of ferric chloride to PAA is 1:1, and the mass-to-volume ratio of ferric chloride to DEG is 1:45 mol/L;
(2) cisplatin Loading
The cisplatin loading method comprises the steps of mixing silver nitrate and cisplatin according to the molar ratio of 1:1, reacting at 40 ℃ to obtain hydrated cisplatin, adding the hydrated cisplatin into the iron oxide nanoparticles for reaction, mixing the hydrated cisplatin and the iron oxide nanoparticles according to the mass ratio of 3:3, and reacting for 2 hours by magnetic stirring to obtain cisplatin-loaded iron oxide nanoparticles;
(3) dopamine coating
Dispersing the cis-platinum carried iron oxide nanoparticles prepared in the step (2) into a dopamine aqueous solution with the pH value of 8.4, wherein the mass ratio of the cis-platinum carried iron oxide nanoparticles to dopamine is 3:1, the concentration of the cis-platinum carried iron oxide nanoparticles in the dopamine aqueous solution is 10mg/L, coating is carried out for 2 minutes, and then, the dopamine-coated cis-platinum-loaded iron oxide nanoparticles are obtained through ultrafiltration;
(4) PEG modification
Adding the iron oxide nanoparticles prepared in the step (3) into a Tris-HCl solution, and adding NH2-PEG-Alkyne in ultrapure water and then mixing the two, NH2The mass ratio of the PEG-Alkyne to the iron oxide nanoparticles is 2:2, and the PEG-modified, dopamine-coated and cisplatin-loaded iron oxide nanoparticles are obtained through ultrafiltration after reaction;
(5) small peptide coupling
Mixing the iron oxide nanoparticles prepared in the step (4) with EGFR receptor targeting small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) Mixing, performing coupling reaction at 30 deg.C for 0.1h while adding CuSO4Solution and NaVc solution, CuSO4The concentration is 20mmol/mL, the concentration of NaVc in the NaVc solution is 60mmol/mL, and the iron oxide nanoparticles which are coupled with small peptides, modified by PEG, coated by dopamine and loaded by cisplatin are obtained, wherein m is 2; the PEG-modified dopamine-coated cisplatin-loaded iron oxide nanoparticles, small peptides and CuSO4The mass ratio of NaVc to NaVc is 1.5:0.2:0.1: 0.24;
(6)64cu nuclide labeling
Mixing the iron oxide nanoparticles prepared in the step (5) with64Cu reacts via the catechol group on dopamine with64In CuCl64Carrying out Cu chelation reaction at the temperature of 30 ℃ for 1h to obtain64Cu-labeled, 11 small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles represented by GE11-64CuPt-PDA@FeyOxI.e. the lung cancer targeted radioactive nanoparticles.
Example 3
A tumor EGFR receptor targeted radioactive nanoparticle is prepared by the following method:
(1) preparation of the support
Adding ferric chloride, polyacrylic acid (PAA) and diethylene glycol (DEG) into NaOH solution dissolved in DEG rapidly at 240 ℃, reacting for 5min, and cooling to obtain iron oxide nanoparticles, wherein the molar ratio of ferric chloride to PAA is 1:3, and the mass-to-volume ratio of ferric chloride to DEG is 1:55 mol/L;
(2) cisplatin Loading
The cisplatin loading method comprises the steps of mixing silver nitrate and cisplatin according to the molar ratio of 5:1, reacting at 60 ℃ to obtain hydrated cisplatin, adding the hydrated cisplatin into the iron oxide nanoparticles for reaction, mixing the hydrated cisplatin and the iron oxide nanoparticles according to the mass ratio of 3:6, and reacting for 0.5h through magnetic stirring to obtain cisplatin-loaded iron oxide nanoparticles;
(3) dopamine coating
Dispersing the cis-platinum carried iron oxide nanoparticles prepared in the step (2) into a dopamine aqueous solution with the pH value of 8.4, wherein the mass ratio of the cis-platinum carried iron oxide nanoparticles to dopamine is 8:1, the concentration of the cis-platinum carried iron oxide nanoparticles in the dopamine aqueous solution is 100mg/L, coating is carried out for 2 minutes, and then, the dopamine-coated cis-platinum-loaded iron oxide nanoparticles are obtained through ultrafiltration;
(4) PEG modification
Adding the iron oxide nanoparticles prepared in the step (3) into a Tris-HCl solution, and adding NH2-PEG-Alkyne in ultrapure water and then mixing the two, NH2The mass ratio of the PEG-Alkyne to the iron oxide nanoparticles is 2:4, and the PEG-modified, dopamine-coated and cisplatin-loaded iron oxide nanoparticles are obtained through ultrafiltration after reaction;
(5) small peptide coupling
Mixing the iron oxide nanoparticles prepared in the step (4) with EGFR receptor targeting small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) Mixing, performing coupling reaction at 60 deg.C for 0.1h while adding CuSO4Solution and NaVc solution, CuSO4The concentration is 40mmol/mL, the concentration of NaVc in the NaVc solution is 120mmol/mL,obtaining small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles, wherein m is 9; the PEG-modified dopamine-coated cisplatin-loaded iron oxide nanoparticles, small peptides and CuSO4The mass ratio of NaVc to NaVc is 1.5:0.2:0.1: 0.24;
(6)64cu nuclide labeling
Mixing the iron oxide nanoparticles prepared in the step (5) with64Cu reacts via the catechol group on dopamine with64In CuCl64Cu chelation reaction is carried out at the temperature of 45 ℃ for 0.1h to obtain64Cu-labeled, 11 small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles represented by GE11-64CuPt-PDA@FeyOxI.e. the lung cancer targeted radioactive nanoparticles.
The effect of the radioactive nanoparticles obtained in the above examples is as follows
The foregoing detailed description of the preferred embodiments of the invention has been presented. It should be understood that numerous modifications and variations could be devised by those skilled in the art in light of the present teachings without departing from the inventive concepts. When Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3When m is 3-9, the material property is similar to that of m 2, and Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH) in the first embodiment can be simply replaced2)2-N3And achieve similar effects. Therefore, the technical solutions available to those skilled in the art through logic analysis, reasoning and limited experiments based on the prior art according to the concept of the present invention should be within the scope of protection defined by the claims.
Claims (10)
1. A tumor EGFR receptor-targeted radioactive nanoparticle, characterized by:
the nano-particles comprise a carrier, a drug, a surface modification molecule and a tumor targeting moleculeAnd a radionuclide, wherein the mass ratio of the carrier, the drug, the surface modification molecule and the tumor targeting molecule is 1-2: 0.2-0.8: 1-2: 0.1-0.5, and the dosage of the radionuclide is 56MBq/m3；
The carrier is iron oxide nano-particles, and the diameter of the iron oxide nano-particles is 5-10 nm;
the drug is cisplatin, is a broad-spectrum antitumor drug, and has a chemical formula of [ Pt (NH)2)]Cl2；
The surface modification molecules are one or more of polyacrylic acid, dopamine and PEG;
the tumor EGFR targeting molecule is a small peptide containing tyrosine-histidine-tryptophan-tyrosine-glycine-tyrosine-threonine-proline-glutamine-asparagine-valine-isoleucine-lysine-azidoacetic acid;
the radionuclide is copper-64.
2. The tumor EGFR receptor-targeted radioactive nanoparticle according to claim 1, wherein the iron oxide nanoparticle is an iron oxide nanoparticle, a ferroferric oxide nanoparticle, or a mixture of two of the foregoing.
3. The tumor EGFR receptor-targeted radioactive nanoparticle according to claim 1, wherein the polyacrylic acid has a molecular weight of 1000-8H11NO2The PEG is PEG (NH) with one end being amino and the other end being alkynyl modified2PEG-Alkyne) with a molecular weight of 1000-.
4. The tumor EGFR receptor-targeted radioactive nanoparticle according to claim 1, wherein the small peptide comprising tyrosine-histidine-tryptophan-tyrosine-glycine-tyrosine-threonine-proline-glutamine-asparagine-valine-isoleucine-lysine-azidoacetic acid has the formula Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3Wherein m is 2-9.
5. The method for preparing tumor EGFR receptor-targeted radioactive nanoparticles according to any one of claims 1 to 4, comprising the steps of:
(1) preparation of the support
The iron oxide nanoparticles are prepared by reacting ferric chloride, polyacrylic acid and diethylene glycol to obtain iron oxide nanoparticles;
(2) cisplatin Loading
The cisplatin loading method comprises the steps of activating cisplatin by silver nitrate to obtain hydrated cisplatin, and then adding the hydrated cisplatin into the iron oxide nanoparticles for reaction to obtain the cisplatin-loaded iron oxide nanoparticles;
(3) dopamine coating
Dispersing the cisplatin-carried iron oxide nanoparticles prepared in the step (2) into dopamine aqueous solution with the pH value of 8.4, coating for 2-30 minutes, and then performing ultrafiltration to obtain dopamine-coated cisplatin-carried iron oxide nanoparticles;
(4) PEG modification
Reacting NH2Adding the PEG-Alkyne solution into the solution containing the iron oxide nanoparticles prepared in the step (3), and performing ultrafiltration after reaction to obtain PEG-modified, dopamine-coated and cisplatin-loaded iron oxide nanoparticles;
(5) small peptide coupling
Mixing the iron oxide nanoparticles prepared in the step (4) with EGFR receptor targeting small peptide (Y-H-W-Y-G-Y-T-P-Q-N-V-I-K- (CH)2)m-N3) Coupling to obtain small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles, wherein m is 2-9;
(6)64cu nuclide labeling
Mixing the iron oxide nanoparticles prepared in the step (5) with64Cu reacts via the catechol group on dopamine with64In CuCl64Cu chelating reaction to obtain64Cu-labeled, 11 small peptide coupling, PEG modification, dopamine coating and cisplatin-loaded iron oxide nanoparticles represented by GE11-64CuPt-PDA@FeyOxI.e. the lung cancer targeted radioactive nanoparticles.
6. The method of claim 5, wherein the tumor EGFR receptor-targeting radioactive nanoparticle is prepared by: the pH of all steps was adjusted with Tris-Tricine buffer at pH 8.5.
7. The method of claim 5, wherein the tumor EGFR receptor-targeting radioactive nanoparticle is prepared by: in the step (1), ferric chloride, polyacrylic acid (PAA) and diethylene glycol (DEG) are used, NaOH solution dissolved in DEG is rapidly added at the temperature of 180-240 ℃, the reaction is carried out for 5-15min, and the iron oxide nanoparticles are prepared after cooling, wherein the molar ratio of the ferric chloride to the PAA is 1 (1-3), and the mass volume ratio of the ferric chloride to the DEG is 1:45-55 mol/L.
8. The method of claim 5, wherein the tumor EGFR receptor-targeting radioactive nanoparticle is prepared by: the silver nitrate activated cisplatin in the step (2) is prepared by mixing silver nitrate and cisplatin according to a molar ratio of 1-5: 1, and reacting at 40-60 ℃ to obtain hydrated cisplatin; the cis-platinum hydrate and the iron oxide nanoparticles are mixed according to the mass ratio of 3: 3-6, and are stirred and reacted for 0.5-2 hours through magnetic stirring to obtain the cis-platinum-loaded iron oxide nanoparticles.
9. The method of claim 5, wherein the tumor EGFR receptor-targeting radioactive nanoparticle is prepared by: in the step (3), the mass ratio of the cisplatin-carried iron oxide nanoparticles to the dopamine is 3-8: 1; the concentration range of the cisplatin-carried iron oxide nanoparticles in the dopamine aqueous solution is 10-100 mg/L;
the solution containing the iron oxide nanoparticles prepared in the step (3) in the step (4) is prepared by adding the iron oxide nanoparticles into a Tris-HCl solution, NH2The PEG-Alkyne solution is prepared by reacting NH2-PEG-Alkyne in ultrapure water and then mixing the two, NH2The mass ratio of the PEG-Alkyne to the iron oxide nanoparticles is 2: 2-4.
10. The method of claim 5, wherein the tumor EGFR receptor-targeting radioactive nanoparticle is prepared by: CuSO is also added in the coupling reaction in the step (5)4Mixing the solution and NaVc solution with the PEG-modified, dopamine-coated and cisplatin-loaded iron oxide nanoparticles and small peptides prepared in the step 4), and stirring and reacting at 30-60 ℃ for 0.1-1 h; the CuSO4The concentration is 20-40mmol/mL, and the concentration of NaVc in the NaVc solution is 60-120 mmol/mL; the PEG-modified dopamine-coated cisplatin-loaded iron oxide nanoparticles, small peptides and CuSO4The mass ratio of NaVc to NaVc is 1.5:0.2:0.1: 0.24;
the chelating reaction in the step (6) has the reaction temperature of 30-45 ℃ and the reaction time of 0.1-1 h.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113092784A (en) * | 2021-04-06 | 2021-07-09 | 中国科学院深圳先进技术研究院 | Functionalized magnetic bead and bioorthogonal chemistry macromolecule one-step capturing method adopting same |
| CN113797359A (en) * | 2021-09-09 | 2021-12-17 | 宁波大学医学院附属医院 | bTiO mediated by IGF 1receptor2Pancreatic cancer diagnosis and treatment nano probe construction method and performance verification method |
| WO2023041639A3 (en) * | 2021-09-15 | 2023-05-19 | Centre National De La Recherche Scientifique | Nanoparticles comprising at least one metal salt and at least one peptide |
| CN116444620A (en) * | 2022-12-28 | 2023-07-18 | 南方医科大学南方医院 | Specific EGFR polypeptide-targeted radiopharmaceuticals, and preparation method and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104984371A (en) * | 2015-07-17 | 2015-10-21 | 上海交通大学 | Tumor targeted radioactive nano-particles and preparation method thereof |
| CN106432594A (en) * | 2016-09-29 | 2017-02-22 | 温州生物材料与工程研究所 | Light- heat-magnetism multi-responsive microgel and preparation method thereof |
| CN106474473A (en) * | 2016-10-12 | 2017-03-08 | 湖北工业大学 | A kind of Fe modified based on gadolinium3O4The preparation of the photo-thermal diagnosis agent of@PDA nano material |
| CN107213137A (en) * | 2017-06-21 | 2017-09-29 | 西南大学 | Pegylation wraps up the preparation method of poly-dopamine drug loaded magnetic nano particle |
| CN109091674A (en) * | 2018-09-14 | 2018-12-28 | 黄冈师范学院 | A kind of multi-functional drug carriers and the preparation method and application thereof |
-
2018
- 2018-12-29 CN CN201811645321.1A patent/CN111374960A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104984371A (en) * | 2015-07-17 | 2015-10-21 | 上海交通大学 | Tumor targeted radioactive nano-particles and preparation method thereof |
| CN106432594A (en) * | 2016-09-29 | 2017-02-22 | 温州生物材料与工程研究所 | Light- heat-magnetism multi-responsive microgel and preparation method thereof |
| CN106474473A (en) * | 2016-10-12 | 2017-03-08 | 湖北工业大学 | A kind of Fe modified based on gadolinium3O4The preparation of the photo-thermal diagnosis agent of@PDA nano material |
| CN107213137A (en) * | 2017-06-21 | 2017-09-29 | 西南大学 | Pegylation wraps up the preparation method of poly-dopamine drug loaded magnetic nano particle |
| CN109091674A (en) * | 2018-09-14 | 2018-12-28 | 黄冈师范学院 | A kind of multi-functional drug carriers and the preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 孙少平著: "《高分子材料在纳米给药系统中的应用》", 31 August 2017, 黑龙江大学出版社 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113092784A (en) * | 2021-04-06 | 2021-07-09 | 中国科学院深圳先进技术研究院 | Functionalized magnetic bead and bioorthogonal chemistry macromolecule one-step capturing method adopting same |
| CN113092784B (en) * | 2021-04-06 | 2023-09-08 | 中国科学院深圳先进技术研究院 | One-step capturing method and application of macromolecules by adopting functionalized magnetic beads to carry out bio-orthogonal chemistry |
| CN113797359A (en) * | 2021-09-09 | 2021-12-17 | 宁波大学医学院附属医院 | bTiO mediated by IGF 1receptor2Pancreatic cancer diagnosis and treatment nano probe construction method and performance verification method |
| CN113797359B (en) * | 2021-09-09 | 2022-12-23 | 宁波大学医学院附属医院 | bTiO mediated by IGF 1receptor 2 Construction method and performance verification method of pancreatic cancer diagnosis and treatment nano probe |
| WO2023041639A3 (en) * | 2021-09-15 | 2023-05-19 | Centre National De La Recherche Scientifique | Nanoparticles comprising at least one metal salt and at least one peptide |
| CN116444620A (en) * | 2022-12-28 | 2023-07-18 | 南方医科大学南方医院 | Specific EGFR polypeptide-targeted radiopharmaceuticals, and preparation method and application thereof |
| CN116444620B (en) * | 2022-12-28 | 2023-11-07 | 南方医科大学南方医院 | Specific EGFR polypeptide-targeted radiopharmaceuticals, and preparation method and application thereof |
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