CN111888472A - Magnetic particle modified hollow gold nanoparticle and preparation method and application thereof - Google Patents
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- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
- A61K49/1824—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles coated or functionalised nanoparticles
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- B22F1/00—Metallic powder; Treatment of metallic powder, e.g. to facilitate working or to improve properties
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- B22F9/00—Making metallic powder or suspensions thereof
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- B22F9/18—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds
- B22F9/24—Making metallic powder or suspensions thereof using chemical processes with reduction of metal compounds starting from liquid metal compounds, e.g. solutions
Abstract
The invention relates to the technical field of medical nano materials, in particular to magnetic particle modified hollow gold nanoparticles and a preparation method and application thereof. According to the hollow gold nanoparticle modified by the magnetic particles, the magnetic particles are wrapped on the outer layer of the hollow gold nanoparticle and filled in the pores of the hollow gold nanoparticle, under the condition that the hollow gold nanoparticle is loaded with the drug, the magnetic particles can play a gating role and can prevent premature drug release, after the drug carrier reaches a pathological change part, under the irradiation of near infrared light, the magnetic particles are separated from the hollow gold nanoparticle due to the electric ion vibration and the thermal effect of the gold nanoparticle, and the loaded drug can be rapidly released from the pores of the hollow gold nanoparticle to a pathological change tissue, so that the treatment effect is improved, and the damage to normal cells is reduced.
Description
Technical Field
The invention relates to the technical field of medical nano materials, in particular to magnetic particle modified hollow gold nanoparticles and a preparation method and application thereof.
Background
Cancer is the most major health problem worldwide, while chemotherapy is one of the most common methods in current anti-cancer treatment, but the traditional chemotherapy has the side effects of killing normal cells, damaging the immune system of a human body and easily relapsing. To reduce these side effects and improve therapeutic efficacy, researchers have focused on developing drug-loaded nanoparticles and on nanoparticle-based targeted anticancer drug delivery systems.
In a targeted drug delivery system based on nanoparticles, a reasonably designed and effective drug carrier is a key technology, and the most ideal drug carrier has a good space, time and dosage control function, for example, when the drug carrier wanders in the blood stream, the drug should be perfectly stored, but when the drug carrier reaches a diseased part, the drug should be rapidly released, so that the treatment effect is maximized and the damage to normal cells is reduced, and therefore, the drug needs to be controlled and prevented from being released in advance before reaching the diseased part, and the reduction of the bioavailability of the drug is caused.
On the other hand, in the course of nanoparticle-based anticancer therapy, the in vivo distribution of nanoparticles and the therapeutic effect of tumor should be accurately monitored. Current imaging techniques do not have sufficient spatial resolution for accurate cancer diagnosis and all imaging techniques require contrast agents. Moreover, the multi-modality imaging modality better reflects the overall and reliable information of the tumor structurally and functionally than a single imaging modality.
Photothermal therapy is a method for treating cancer by generating heat at a tumor part by using near infrared light and a photosensitive material, and the photothermal therapy and a targeted drug delivery technology are combined, so that the treatment effect of cancer can be further improved, in the prior art, the controlled release of a drug is realized while the targeted drug delivery technology by using a photosensitive effect is utilized, for example, in Chinese patent CN109453378A, the drug is controlled and released under the action of light by arranging a photoresponsive polymer shell structure, but the drug carrier disclosed in the patent cannot be used as a multi-mode imaging contrast agent.
Therefore, it is necessary to develop a multifunctional drug carrier with drug loading, controlled drug release, multi-modal imaging contrast agent, etc., so that the treatment of cancer can be integrated with treatment and diagnosis, the treatment effect can be improved, the side effect can be reduced, and the treatment cost and the life quality of patients can be reduced.
Currently, the technology related to the superparamagnetic modified hollow gold nanoparticle drug carrier is U.S. patent (US20200114420a 1); methods of Producing Cobalt Nanoparticles and Hollow gold Nanoparticles and Kits for Practicing Same and Korean patent (1020150074861); high active magnetic silica nanoparticles for separating biological and method for preparing the same are disclosed in the patent relating to the technology of preparing hollow gold nanoparticles and superparamagnetic iron.
However, the nanoparticles produced by these prior art techniques can only be used as single modality imaging contrast agents and lack the design of anticancer drug delivery and controlled drug release, for example; the wandering time in the human body is enhanced, the sufficient drug load is realized, the drug controlled release is reasonable, and the like. Therefore, there is a need to develop nanoparticles that can be used as contrast agents for multi-modal imaging, and can deliver drugs and release drugs in a targeted manner under the action of photothermal and photodynamic therapy, so as to improve the diagnosis and treatment effects of solid tumors.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention aims to provide the magnetic particle modified hollow gold nanoparticles, which can effectively control the release of the medicament, avoid the premature release of the medicament, improve the utilization rate of the medicament and be used as a dual contrast agent of MRI and CT.
The second purpose of the invention is to provide a preparation method of the hollow gold nanoparticles modified by the magnetic particles.
Meanwhile, the invention also provides application of the magnetic particle modified hollow gold nanoparticles
The hollow gold nanoparticles modified by the magnetic particles are formed by wrapping the magnetic particles on the outer layer of the hollow gold nanoparticles, wherein the magnetic particles are filled in the pore structures of the hollow gold nanoparticles.
Optionally, the hollow gold nanoparticles are loaded with drugs and can be used as drug carriers for preparing targeted drugs.
Optionally, the magnetic particles are superparamagnetic particles; the surfaces of the hollow gold nanoparticles are modified with amino groups; the superparamagnetic iron particles are hydrophilic Fe with the size of 5-10 nm3O4Nanoparticles. Optionally, the hollow gold nanoparticles with the amino groups modified on the surfaces are prepared by modifying the surfaces of amino-rich 2-aminoethanethiol or polyethyleneimine.
Optionally, the shape of the super paramagnetic iron comprises a sphere, a cube, an octahedron, a tetrahedron, a rod, or a derivative structure thereof.
Optionally, the diameter of the hollow gold nanoparticles is 50-200 nm; and carrying out pegylation treatment on the surfaces of the hollow gold nanoparticles modified by the magnetic particles. Optionally, the drug is selected from one or more of doxorubicin (doxorubicine), Epirubicin (Epirubicin), gemcitabine (gemcitabin), Cisplatin (cisclin), Carboplatin (Carboplatin), Procarbazine (Procarbazine), Cyclophosphamide (Cyclophosphamide), Dactinomycin (Dactinomycin), Daunorubicin (Daunorubicin), Etoposide (Etoposide), Tamoxifen (Tamoxifen), Mitomycin (Mitomycin), Bleomycin (Bleomycin), Plicamycin (Plicamycin), Vinblastine (vinblasttine), and Methotrexate (Methotrexate).
According to the hollow gold nanoparticle modified by the magnetic particles, the magnetic particles are wrapped on the outer layer of the hollow gold nanoparticle and filled in the pores of the hollow gold nanoparticle, under the condition that the hollow gold nanoparticle is loaded with the drug, the magnetic particles can play a gating role and can prevent premature drug release, after the drug carrier reaches a pathological change part, under the irradiation of near infrared light, the magnetic particles are separated from the hollow gold nanoparticle due to the electric ion vibration and the thermal effect of the gold nanoparticle, and the loaded drug can be rapidly released from the pores of the hollow gold nanoparticle to a pathological change tissue, so that the treatment effect is improved, and the damage to normal cells is reduced.
The preparation method of the hollow gold nanoparticles modified by the magnetic particles comprises the following operation steps:
1) preparation of hydrophilic Fe3O4Nanoparticles;
2) preparing hollow gold nanoparticles with amino groups modified on the surfaces;
3) mixing the hollow gold nanoparticle solution with the surface modified with the amino group prepared in the step 2) with a drug solution to prepare drug-loaded hollow gold nanoparticles;
4) mixing the hollow gold nanoparticle solution loaded with the drug prepared in the step 3) and the hydrophilic Fe prepared in the step 1)3O4And mixing the nano particle solutions to prepare the magnetic particle modified hollow gold nano particles.
Optionally, preparing hydrophilic Fe in step 1)3O4The specific method of the nano particles is as follows:
10mmol of iron (III) chloride and 5mmol of iron (II) chloride were dissolved in 24 ml of aqueous hydrochloric acid (HCl 1M). Then, under the protection of dry nitrogen, dropwise adding the solution into NaOH 1M aqueous solution, mechanically stirring for 60 minutes at normal temperature, adding 3-5 g of Citric Acid (CA), mechanically stirring for 30 minutes at 80 ℃, performing magnetic separation on black precipitates, washing for 3 times by using deionized water, ultrasonically shaking the solution for 10 minutes, and then centrifuging at 1000-3000 rpm/min to remove large particles and/or undispersed residues.
Optionally, the specific method for preparing the hollow gold nanoparticles with the surface modified with the amino group in the step 2) comprises the following steps:
0.5mM trisodium citrate (C) was mixed in 400ml distilled water6H5Na3O7·2H2O), 0.2mM silver nitrate (AgNO)3) And 0.4ml of 1.0mM sodium borohydride (NaBH)4) Synthesizing silver nano particles. In NaBH4After complete hydrolysis, 0.4ml of 2.0M hydroxylamine hydrochloride (NH) was added to the solution2OH HCl) and 1ml of 0.1M AgNO3Stirring overnight at a temperature of 0-40 ℃ and a rotation speed of 400-1000 rpm/min.
Then 2.4ml to 4ml of 25mM tetrachlorouric acid trihydrate (HAuCl) was added at 60 ℃4) Hollow gold nanoparticles (Hollow gold nanoparticles; HGN). In order to obtain the aminated derivative of HGN, HGN (1mg/ml) and 2-aminoethanethiol (2mg/ml) are stirred for 24 hours in PBS buffer solution, and then the mixture is centrifuged and concentrated to obtain hollow gold nanoparticles with amino groups modified on the surfaces, namely the aminated derivative of HGN, namely HGN-NH2。
It should be understood that 2-aminoethanethiol as the aminating agent in the above reaction procedure may also be selected from other agents containing amine groups, such as aminated derivatives of HGN obtained by reaction with a solution of polyethyleneimine (MW: 10000 or less) at a concentration of 2 mg/ml.
Optionally, the preparation method further comprises performing surface polyethylene treatment on the hollow gold nanoparticles modified by the magnetic particles: activating carboxylic acid polyethylene glycol by using 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and adding the solution after reaction into the magnetic particle modified hollow gold nanoparticle solution.
The hollow gold nanoparticles modified by the magnetic particles can be applied to the preparation of diagnostic agents and/or therapeutic agents; further, compounds and/or drugs for use in diagnostic imaging or imaging-aiding applications. Specifically, the surface of the gold nanoparticles is covered with magnetic particles, so that the gold nanoparticles can be used as a computed tomography CT imaging contrast agent and a magnetic resonance MRI imaging contrast agent. Meanwhile, the hollow structure of the gold nanoparticles can be loaded with drugs.
Drawings
FIG. 1 is a schematic diagram of a process for preparing drug-loaded magnetic particle-modified hollow gold nanoparticles according to an embodiment of the present invention;
FIG. 2 is a transmission electron microscope photograph of hollow gold nanoparticles with unmodified magnetic particles prepared according to an example of the present invention;
FIG. 3 is a transmission electron microscope photograph of superparamagnetic particles prepared according to an embodiment of the present invention;
FIG. 4 is a transmission electron microscope picture of drug-loaded superparamagnetic particle-modified hollow gold nanoparticles prepared in the present example;
FIG. 5 is a transmission electron microscope picture of drug-loaded superparamagnetic particle-modified hollow gold nanoparticles prepared according to an embodiment of the present invention after near-infrared irradiation.
Detailed Description
The present invention will be described in further detail with reference to specific examples. The equipment and reagents used in the examples and the experimental examples were commercially available except as specifically indicated.
Examples
In this embodiment, a process flow chart of the preparation of the hollow gold nanoparticles modified by drug-loaded superparamagnetic particles is shown in fig. 1, and the specific preparation method is as follows:
1) preparation of superparamagnetic iron granules (SPIO)
Hydrophilic superparamagnetic iron (SPIO) was synthesized by a chemical coprecipitation method. 10mmol of iron (III) chloride and 5mmol of iron (II) chloride were dissolved in 24 ml of aqueous hydrochloric acid (HCl 1M). Then, the solution was added dropwise to a 1M aqueous solution of NaOH under a dry nitrogen blanket, and mechanically stirred at room temperature for 60 minutes. Subsequently, 5g of Citric acid (Citric acid; CA) was added and mechanically stirred at 80 ℃ for 30 minutes. The black precipitate was subjected to magnetic separation, washed three times with anhydrous ethanol, and then dispersed in 20ml of dichloromethane. The solution was sonicated for 10 minutes and then centrifuged to remove undispersed residue (2000 rpm, 10 minutes) to produce SPIO. The SPIO was obtained by successful preparation as shown in the transmission electron microscope picture of fig. 3.
2) Preparation of Hollow Gold Nanoparticles (HGN)
0.5mM trisodium citrate (C) is first mixed in 400ml of distilled water6H5Na3O7·2H2O), 0.2mM silver nitrate (AgNO)3) And 0.4ml of 1.0mM sodium borohydride (NaBH)4) Synthesizing silver nano particles. In NaBH4After complete hydrolysis, 0.4ml of 2.0M hydroxylamine hydrogen chloride (NH) was added to the solution2OH HCl) and 1ml of 0.1M AgNO3And stirred overnight. Then by adding 2.4ml of 25mM tetrachlorouric acid trihydrate (HAuCl) at 60 deg.C4) To form Hollow gold nanoparticles (Hollow gold nanoparticles; HGN).
To obtain an aminated derivative of HGN, HGN (1mg/ml) was stirred with 2-aminoethanethiol (2mg/ml) in PBS buffer for 24 hours, and concentrated by centrifugation to give HGN-NH2. As shown in a transmission electron microscope picture of figure 2, the hollow gold nanoparticles are successfully prepared and obtained by characterization.
3) Preparation of superparamagnetic iron particle modified hollow gold nanoparticles (HGN/DOX @ SPIO-PEG)
Doxorubicin (DOX) -loaded hollow gold nanoparticles (HGN/DOX) were first prepared and 1ml of DOX solution (1mg/ml) was added to 3ml of HGN-NH2(1mg/ml) solution. After stirring for 24 hours, centrifuging at 10000rpm/min for 5 minutes, recovering HGN/DOX, and obtaining HGN/DOX @ SPIO by mixing the SPIO solution and the HGN/DOX solution (1: 5), stirring for 2 hours, and centrifuging (10000 rpm/min). Activating carboxylic acid polyethylene glycol (PEG-COOH, MW2000) in 10ml PBS by using 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) according to a molar mass ratio of 1:1:1, reacting for 1h, adding the solution into the PBS solution dispersed with HGN/DOX @ SPIO, stirring for 3h, and finally, recovering HGN/DOX @ SPIO-PEG through centrifugation, thus completing the preparation of the hollow gold nanoparticles modified by the magnetic particles loaded with the drugs. And as shown in a transmission electron microscope picture of fig. 4, the hollow gold nanoparticles modified by the superparamagnetic particles are successfully prepared and obtained.
It will be appreciated that it is also possible to use other aminating agents than 2-aminoethanethiol in step 2) in order to obtain the aminated derivative of HGN, such as polyethyleneimines (MW: 10000 or less);
the drug doxorubicin DOX in step 3) may also be one or more of other drug components, such as Epirubicin (Epirubicin), gemcitabine (gemcitabin), Cisplatin (cissplatin), Carboplatin (Carboplatin), Procarbazine (Procarbazine), Cyclophosphamide (Cyclophosphamide), Dactinomycin (Dactinomycin), Daunorubicin (Daunorubicin), Etoposide (Etoposide), Tamoxifen (Tamoxifen), Mitomycin (Mitomycin), Bleomycin (Bleomycin), Plicamycin (Plicamycin), Vinblastine (vinblastatin), Methotrexate (Methotrexate).
The surface of the gold nanoparticles prepared by the embodiment of the invention is covered with magnetic particles, so that the gold nanoparticles can be used as a CT imaging contrast agent for computed tomography and can also be used as a MRI imaging contrast agent.
Test examples
In order to characterize that the hollow gold nanoparticles modified by the superparamagnetic particles prepared in the embodiment of the present invention can effectively control release of a drug, and avoid the drug being released in advance, the hollow gold nanoparticles modified by the superparamagnetic particles loaded with DOX prepared in the above embodiment are subjected to an infrared action for a period of time, and then the morphological structure of the hollow gold nanoparticles is observed through a transmission electron microscope, as shown in fig. 5, the superparamagnetic particles characterized on the surface fall off from the surface of the hollow gold nanoparticles to expose the pores of the hollow gold nanoparticles, so that the drug is rapidly released from the pores of the hollow gold nanoparticles, thereby realizing effective control of drug release.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. The hollow gold nanoparticle modified by the magnetic particles is characterized by being formed by wrapping the magnetic particles on the outer layer of the hollow gold nanoparticle, wherein the magnetic particles are filled in the pore structure of the hollow gold nanoparticle.
2. The magnetic particle-modified hollow gold nanoparticle of claim 1, wherein the hollow gold nanoparticle is loaded with a drug.
3. The magnetic-particle-modified hollow gold nanoparticles of claim 1 or 2, wherein the magnetic particles are superparamagnetic particles; the surfaces of the hollow gold nanoparticles are modified with amino groups; the superparamagnetic iron particles are hydrophilic Fe with the size of 5-10 nm3O4Nanoparticles.
4. The magnetic particle-modified hollow gold nanoparticle of claim 3, wherein the morphology of the superparamagnetic iron comprises a sphere, a cube, an octahedron, a tetrahedron, a rod, or a derivative thereof.
5. The magnetic particle-modified hollow gold nanoparticle according to claim 1 or 2, wherein the diameter of the hollow gold nanoparticle is 50 to 200 nm; and carrying out pegylation treatment on the surfaces of the hollow gold nanoparticles modified by the magnetic particles.
6. The magnetic particle-modified hollow gold nanoparticles of claim 2, wherein the drug is selected from one or more of doxorubicin (doxorubicine), Epirubicin (Epirubicin), gemcitabine (gemcitabin), Cisplatin (cispain), Carboplatin (Carboplatin), Procarbazine (Procarbazine), Cyclophosphamide (Cyclophosphamide), Dactinomycin (Dactinomycin), Daunorubicin (Daunorubicin), Etoposide (Etoposide), Tamoxifen (Tamoxifen), Mitomycin (Mitomycin), Bleomycin (Bleomycin), Plicamycin (Plicamycin), Vinblastine (vinblastatin), Methotrexate (Methotrexate).
7. The method for preparing magnetic particle-modified hollow gold nanoparticles according to claim 3, comprising the following steps:
1) preparation of hydrophilic Fe3O4Nanoparticles;
2) preparing hollow gold nanoparticles with amino groups modified on the surfaces;
3) mixing the hollow gold nanoparticle solution with the surface modified with the amino group prepared in the step 2) with a drug solution to prepare drug-loaded hollow gold nanoparticles;
4) mixing the hollow gold nanoparticle solution loaded with the drug prepared in the step 3) and the hydrophilic Fe prepared in the step 1)3O4And mixing the nano particle solutions to prepare the magnetic particle modified hollow gold nano particles.
8. The method of claim 7, further comprising performing surface polyethylene treatment on the magnetic particle modified hollow gold nanoparticles: activating carboxylic acid polyethylene glycol by using 1- (3-dimethylaminopropyl) -3-ethyl carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and adding the solution after reaction into the magnetic particle modified hollow gold nanoparticle solution.
9. Use of magnetic particle-modified hollow gold nanoparticles according to any one of claims 1 to 6 for the preparation of diagnostic and/or therapeutic agents.
10. Use according to claim 9, for compounds and/or drugs in diagnostic imaging or imaging-aid applications.
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110311822A1 (en) * | 2010-06-16 | 2011-12-22 | Board Of Regents, The University Of Texas System | Hollow nanoparticles and nanocomposites and methods of making hollow nanoparticles and nanocomposites |
CN102805870A (en) * | 2012-05-25 | 2012-12-05 | 天津大学 | Gold nano-spherical shell carrier with procedural gene drug release property and preparation method |
CN103301473A (en) * | 2013-05-30 | 2013-09-18 | 天津大学 | Cis-platinum and gold nanoparticle hollow sphere shell carrier compound with light-operated releasing function and preparation method |
CN105056243A (en) * | 2015-07-22 | 2015-11-18 | 郑州大学 | Pharmaceutical composition of hyaluronic acid modified magnetic hollow mesoporous copper sulfide as well as preparation method and application of pharmaceutical composition |
CN107812200A (en) * | 2017-10-21 | 2018-03-20 | 天津大学 | BSA-gadolinium ionic complex-coated hollow gold nanosheet and preparation method thereof |
-
2020
- 2020-09-19 CN CN202010990486.3A patent/CN111888472A/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20110311822A1 (en) * | 2010-06-16 | 2011-12-22 | Board Of Regents, The University Of Texas System | Hollow nanoparticles and nanocomposites and methods of making hollow nanoparticles and nanocomposites |
CN102805870A (en) * | 2012-05-25 | 2012-12-05 | 天津大学 | Gold nano-spherical shell carrier with procedural gene drug release property and preparation method |
CN103301473A (en) * | 2013-05-30 | 2013-09-18 | 天津大学 | Cis-platinum and gold nanoparticle hollow sphere shell carrier compound with light-operated releasing function and preparation method |
CN105056243A (en) * | 2015-07-22 | 2015-11-18 | 郑州大学 | Pharmaceutical composition of hyaluronic acid modified magnetic hollow mesoporous copper sulfide as well as preparation method and application of pharmaceutical composition |
CN107812200A (en) * | 2017-10-21 | 2018-03-20 | 天津大学 | BSA-gadolinium ionic complex-coated hollow gold nanosheet and preparation method thereof |
Non-Patent Citations (2)
Title |
---|
QIANHUA FENG ET AL: ""Programmed near-infrared light-responsive drug delivery system for combined magnetic tumor-targeting magnetic resonance imaging and chemo-phototherapy"", 《ACTA BIOMATERIALIA》 * |
白灵玉: ""基于空心金纳米球的多功能纳米颗粒的制备及其在生物医学中的应用"", 《中国优秀博硕士学位论文全文数据库(硕士) 工程科技Ⅰ辑》 * |
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