CN102989015A - Preparation method of CT imaging molecular probe of folate receptor targeted tumor - Google Patents
Preparation method of CT imaging molecular probe of folate receptor targeted tumor Download PDFInfo
- Publication number
- CN102989015A CN102989015A CN2012105284119A CN201210528411A CN102989015A CN 102989015 A CN102989015 A CN 102989015A CN 2012105284119 A CN2012105284119 A CN 2012105284119A CN 201210528411 A CN201210528411 A CN 201210528411A CN 102989015 A CN102989015 A CN 102989015A
- Authority
- CN
- China
- Prior art keywords
- folic acid
- preparation
- nanometer gold
- gold
- coated
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a preparation method of a CT imaging molecular probe of folate receptor targeted tumors, which comprises the following steps: dissolving folic acid which is used as a wrapping agent in a solution which contains gold ions and is used for preparing nanogold, adjusting the pH to 7.0-7.5 to obtain a mixed solution, wherein the molar ratio of folic acid to gold ions is 1:2-6; adding a reducing agent into the mixed solution, rapidly stirring and reacting for at least 1 hour, naturally cooling after the reaction, performing dialysis to remove unreacted parts so as to obtain the nanogold coated by folic acid. The nanogold coated by folic acid FA-GNP prepared in the invention has high attenuation capability for X ray, and can be used as a CT imaging contrast agent; the FA-GNP can provide CT images with high contrast for tumors.
Description
Technical field
The invention belongs to CT molecular imaging technical field, relate to a kind of preparation method of CT imaging molecular probe of folacin receptor target tumor.
Background technology
Malignant tumor is a kind of disease of common serious harm human health, has become at present one of human main causes of death.In recent years, along with development economic and science and technology, people's living environment and living habit change day by day, and it is in rising trend that tumor has become a difficult problem and its sickness rate of harm humans health in the world wide.Compared with developed countries, the mortality of malignant tumors of China will surpass the world average level.The morning and evening of diagnosis has determined the probability that patient cures, and according to a large amount of clinical data statistics, the five year survival rate of the malignant tumor of early discovery can reach more than 90%, and the discovery in late period only has about 20%.Most of malignant tumor waits when classical symptom and sign having occurred in early days without any symptom, has often belonged to middle and advanced stage and has affected the opportunity for the treatment of adversely.If therefore can realize the early diagnosis of malignant tumor, accurately understanding position, the size of malignant tumor and having or not transfer is very necessary with treatment for the accurate of tumor by stages, will improve to a great extent the cure rate of tumor.Therefore, the earlier detection of tumor and treatment have become the focus that the various countries scientist pays close attention to.
Realize the early diagnosis and therapy of tumor, at first will seek the tumor markers in the living cells, by tumor marker is carried out labelling, carry out again imaging and obtain relevant information.Because folacin receptor (FolicAcid Receptor FR) is at the most tumors surface of cell membrane, such as cervical cancer, ovarian cancer, breast carcinoma, carcinoma of endometrium, pulmonary carcinoma and nasopharyngeal carcinoma etc., overexpression exceeds 20-200 doubly than normal cell usually.And, because the tumor diagnosis and therapy of folate-targeted has pair tumor cell affinity high, circulation time is grown (5-20h) in vivo, the advantage such as can be eliminated very soon in normal structure, folacin receptor usually is used as the target of folic acid medicinal composition and realizes crossing video picture and the treatment of the tumor of expressing FR.
In recent years, along with the develop rapidly of nanotechnology, nano material has become a very vital new direction at the applied research of biomedical engineering field.Because nanoparticle especially nanometer gold has the surface chemistry ability of easy control, the characteristics such as unique optical property and local fields enhancement effect, it is being subject to extensive attention aspect diagnosis of imaging in biological tissues, cancer and the treatment.
CT image acquisition time is short, spatial resolution is high (50-200 μ m), can whole imaging, expense is cheap, consider that with regard to availability, efficient and cost etc. are many-sided CT is one of the most effective diagnostic tool clinically.Existingly contain effectively absorption of x-rays of iodine CT contrast agent, but only have in vivo very short remaining time namely to be removed by kidney, imaging time short (in 15 minutes).And modifiability own is poor, is difficult to and the tumor marker coupling, does not possess targeting.In addition, contain diodone to kidney dis in toxicity, the blood vessel osmotic pressure is high.Nanometer gold has higher X ray damping capacity by comparison, and the body-internal-circulation time is long, and is easy to and the biomolecule combination, can the target tumor cell.
The coated nanometer gold of preparation folic acid also has certain methods at present, such as, (Li GP, the Li D such as Wang, Zhang LX, Zhai JF, Wang EK, one-stop synthesis of Folic Acid protected GoldNanoparticles and Their Receptor-Mediated Intracellular Uptake, Chem.Eur.J., 2009 15:9868-9873) reported a kind ofly under temperate condition, prepared nanogold particle take folic acid as Reducing agent, and have certain advantage.But longer when this method preparation is used.The people such as Sun Liping (Sun Liping, Lai Youqun, Zhang Zhaowu, Ma Yanyan, Jia Jing, the synthetic method of folate receptor targeted type nano gold particles, patent of invention CN:102029401) utilize microwave heating method to prepare the nanogold particle of folic acid parcel.But this method needs special microwave equipment.The prepared particle diameter of two kinds of above-mentioned methods is all inhomogeneous, and whether checking can not be applied to the CT imaging.
Summary of the invention
The problem that the present invention solves is to provide a kind of preparation method of CT imaging molecular probe of folacin receptor target tumor, prepares the nano Au particle as the folic acid parcel of target tumor probe.
The present invention is achieved through the following technical solutions:
The preparation method of the nanometer gold that a kind of folic acid is coated may further comprise the steps:
1) take folic acid as coating agent, folic acid is dissolved in the solution that contains gold ion for the preparation of nanometer gold, and to regulate its pH is 7.0～7.5 that obtain mixed solution, the mol ratio of its Folic Acid and gold ion is 1:5～10;
2) add Reducing agent in mixed solution, then rapid stirring reacts at least 1h, natural cooling after reaction finishes, and unreacted part is removed in dialysis, obtains the coated nanometer gold of folic acid.
The described solution that contains gold ion for the preparation of nanometer gold is chlorauric acid solution.
Folic acid is water-soluble, and heated and stirred makes after the folic acid dissolving, joins in the solution that contains gold ion again.
The concentration of described mixed solution Folic Acid is 0.08～0.24mmol/L, and the concentration of gold ion is 0.4～1.5mmol/L.
Described Reducing agent is sodium borohydride, and the mol ratio of sodium borohydride and gold ion is 520:4～15.
Describedly in mixed solution, add Reducing agent, rapid stirring reaction 2～3h then, mixing speed is 1000～1500 rev/mins.
The preparation method of the nanometer gold that described folic acid is coated is characterized in that, its dialysis of described dialysis is dammed molecular weight greater than the material of 500 ~ 1000D, dialyses 6～12 hours.
The preparation method of the nanometer gold that described folic acid is coated is characterized in that, the particle diameter of the nanometer gold that prepared folic acid is coated is 3～5nm, is in the 3.5%NaCl solution and 25000r/min is centrifugal all coagulation can not occur down in mass concentration.
The application of the preparation method of the nanometer gold that described folic acid is coated in the CT imaging molecular probe of preparation folacin receptor target tumor.
The nanometer gold that prepared folic acid is coated with is as the application of the CT imaging molecular probe of folacin receptor target tumor.
Compared with prior art, the present invention has following useful technique effect:
The preparation method of the nanometer gold that folic acid provided by the invention is coated, take folic acid as stabilizing agent with coating agent, take sodium borohydride as Reducing agent, prepare quickly and easily the nano Au particle (folic acidcoatd gold nanoparticles, FA-GNPs) of folic acid parcel as the target tumor probe.This nano-probe particle size distribution is between 3-5nm, system homogeneous, stable, and all coagulation can not occur under hypersaline environment (3.5%NaCl solution) and high speed centrifugation (25000rpm), and X ray had strong absorption, can the target tumor cell and can carry out blur-free imaging to tumor.
The nanometer gold FA-GNPs that the prepared folic acid of the present invention is coated, to the HepG2 cell surface, and GNPs not can be incorporated into the IMR-90 cell surface in 30min by the FA-FR specific binding.HepG2 cell surface great expression FR, and the IMR-90 cell surface is not expressed FR substantially, shows that there is targeting in prepared FR-GNPs to the FR of tumor cell surface expression.
The coated nanometer gold FA-GNPs of folic acid that the present invention is prepared has higher damping capacity to X ray, can be used as the CT image-forming contrast medium; FA-GNPs can provide for tumor the CT imaging of high-contrast.
Description of drawings
Fig. 1-1 is FA-GNPs TEM photo, and Fig. 1-2 is the particle size distribution figure of FA-GNPs;
Fig. 2-1 is the full spectrogram of the XPs of FA-GNPs;
Fig. 2-2 is the XPS open score of each element among the FA-GNPs, and wherein A is that Au4f, B are that C1s, C are that N1s, D are O1s;
Fig. 3-1 is FA-GNPs and the electromicroscopic photograph of HepG2 cell culture after 30 minutes;
Fig. 3-2 is GNPs and the electromicroscopic photograph of HepG2 cell culture after 30 minutes;
Fig. 4 is the culture fluid absorbance variation diagram before and after the HepG2 cell culture that is added with FA-GNPs;
Fig. 5-1 is that the variable concentrations of each FA-GNPs among Fig. 5-2 distributes;
Fig. 5-2 is the FA-GNPs CT imaging (inverse processing) of the FA-GNP variable concentrations of correspondence;
Fig. 5-3 is the CT value curve of variable concentrations FA-GNPs;
Fig. 6 is the photo that Cervical Tumor is planted respectively in thigh both sides, nude mice back;
Fig. 7 be nude mice from the to the end CT imaging of varying cross-section of tail, view left side is R, the right side is L, "Left"-deviationist when nude mice is put; Arrow indication place is the HepG2 tumor tissues of injecting FA-GNPs.
The specific embodiment
The present invention is described in further detail below in conjunction with specific embodiment, and the explanation of the invention is not limited.
Embodiment 1
The preparation method of the nanometer gold that a kind of folic acid is coated may further comprise the steps:
Take by weighing FA 0.0018g, be dissolved in the 50mL ultra-pure water, drip the HAuCl4 solution of 1mL 1%, at this moment FA and HAuCl
4Mol ratio be 1:6, be placed on the heating stirrer, stirring 5min above (the concrete time does not require that mixing get final product), to adopt concentration be about the NaOH solution regulation system pH value to 7.4 of 1M and 0.1M, solution presents glassy yellow just at this moment, FA all dissolves.
Take by weighing 0.1g NaBH
4, be dissolved in the 2mL ultra-pure water the cold mixture of ice and water that places.FA and HAuCl
4Drip fast NaBH in the mixed liquor
4Solution, solution all present the burgundy color, and rapid stirring 2 hours, and mixing speed is about 1200 rev/mins.Behind the natural cooling, with the sample that obtains in ultra-pure water (dialysis dam the material of molecular weight greater than 500D) 12 hours, remove unreacted molecule, namely obtain the coated Nano-Au probe of folic acid, the sample for preparing is put into 4 ℃ of Refrigerator stores.
Embodiment 2
The preparation method of the nanometer gold that a kind of folic acid is coated may further comprise the steps:
Take by weighing FA 0.0026g, be dissolved in the 50mL ultra-pure water, drip the HAuCl4 solution of 1mL 1%, at this moment FA and HAuCl
4Mol ratio be 1:4, be placed on the heating stirrer, stirring 5min above (the concrete time does not require that mixing get final product), to adopt concentration be about the NaOH solution regulation system pH value to 7.2 of 1M and 0.1M, solution presents glassy yellow just at this moment, FA all dissolves.
Take by weighing 0.12g NaBH
4, be dissolved in the 2mL ultra-pure water the cold mixture of ice and water that places.FA and HAuCl
4Drip fast NaBH in the mixed liquor
4Solution, solution all present the burgundy color, and rapid stirring 2 hours, and mixing speed is about 1500 rev/mins.Behind the natural cooling, the sample that obtains was dialysed 12 hours, remove unreacted molecule, namely obtain the coated Nano-Au probe of folic acid, the sample for preparing is put into 4 ℃ of Refrigerator stores.
Embodiment 3
The preparation method of the nanometer gold that a kind of folic acid is coated may further comprise the steps:
Take by weighing FA 0.0053g, be dissolved in the 50mL ultra-pure water, drip the HAuCl4 solution of 1mL 1%, at this moment FA and HAuCl
4Mol ratio be 1:2, be placed on the heating stirrer, stirring 5min above (the concrete time does not require that mixing get final product), to adopt concentration be about the NaOH solution regulation system pH value to 7.5 of 1M and 0.1M, solution presents glassy yellow just at this moment, FA all dissolves.
Take by weighing 0.13g NaBH
4, be dissolved in the 2mL ultra-pure water the cold mixture of ice and water that places.FA and HAuCl
4Drip fast NaBH in the mixed liquor
4Solution, solution all present the burgundy color, and rapid stirring 3 hours, and mixing speed is about 1000 rev/mins.Behind the natural cooling, the sample that obtains was dialysed 12 hours, remove unreacted molecule, namely obtain the coated Nano-Au probe of folic acid, the sample for preparing is put into 4 ℃ of Refrigerator stores.
The prepared nanoparticle of the present invention passes through electron microscope observation, finds its particle size distribution homogeneous, between 3～5nm, as shown in Figure 1.
By the X ray electron spectroscopy measurement nanometer gold and folic acid in conjunction with situation, shown in Fig. 2-1,2-2.Fig. 2-1 is for the XPS of FA-GNPs composes entirely, in conjunction with what can be produced by Au 4f, C 1s, N 1s and O 1s respectively at the crest at 80-90,280-290,395-405 and 530-540eV place.
Fig. 2-2(B) combination of middle c h bond can actually be measured as 283.15, differs 1.65 with standard value, and therefore the combination of whole power spectrum can be calibrated by+1.65.Among Fig. 2-2(A) in conjunction with can 84.09 and 87.09eV two peaks are arranged, produce by Au0, be respectively Au 4f7/2 and Au 4f5/2, show to exist Au3+ to be reduced in the system; Among Fig. 2-2(C) in conjunction with can 399.12 and the crest of 400.82eV produced by N1s, be respectively-NH2 and-N element among the OCONH, provide by FA; Among Fig. 2-2(D) in conjunction with can 531.78,533.00 and the crest at 534.61eV place may be respectively by-OH ,-COOH and-the OCNH-generation.
The prepared coated nanometer gold FA-GNPs of folic acid of the present invention has tumor cell targeting characteristic.With FA-GNPs and GNPs respectively with the HepG2 cell co-culture, competitive binding occurs in order to prevent FA and FR, cell culture system (especially cell culture fluid) is not all brought FA into.After the 30min, with the unnecessary FA-GNPs of PBS flush away, make the FA-GNPs surface that is combined in the HepG2 surface form silver-colored shell by silver staining enhancement.Cell after silver dyed send scanning electron microscopic observation after glutaraldehyde is fixing, shown in Fig. 3-1,3-2.
Fig. 3-1,3-2 are the electromicroscopic photograph of cultivating respectively the HepG2 cell behind the 30min with FA-GNPs and GNPs, are adsorbing a large amount of whitenesses among Fig. 3-1 on the cell, and are not substantially having on the cell of Fig. 3-2, think the FA-GNPs of these whitenesses for coated silver-colored shell.Sample repeatedly cleans through PBS solution before doing the Electronic Speculum pre-treatment simultaneously, substantially removes unconjugated FA-GNPs and GNPs, and the neat and tidy in the visual field is got rid of the probability that silver-colored granule adsorbs.
Therefore can reach a conclusion: FA-GNPs passes through the FA-FR specific binding to the HepG2 cell surface, and GNPs not can be incorporated into the HepG2 cell surface in 30min.HepG2 cell surface great expression FR, and the IMR-90 cell surface is not expressed FR substantially, there is targeting in the FR-GNPs that proves the present invention's preparation really to the FR of tumor cell surface expression.
FA-GNPs adds cell culture fluid to after a period of time, and FA-GNPs is attached to the HepG cell surface by the specific binding of FA-FR, and the FA-GNPs content in the cell culture fluid reduces, and significantly reduces (see figure 4) before the absorbance at 524nm place is cultivated.
The reduction of absorbance can represent the quantity number of FA-GNPs and HepG2 Cell binding indirectly, qualitatively referred to herein as relative absorbance (Δ A).Wherein, absorbance is 0.63508 before the HepG2 of the 524nm place cell culture; Be 0.40961 behind the cell culture, Δ A=0.22647, illustrate from the side a large amount of FA-GNPs with the HepG2 Cell binding.
The prepared coated nanometer gold FA-GNPs of folic acid of the present invention has higher damping capacity to X ray, can be with it as the CT image-forming contrast medium.Fig. 5-1～5-3 reflects that intuitively FA-GNPs strengthens along with the increase of concentration the damping capacity of X ray, and the CT value of pure water is 0, so do not show stain corresponding to pure water among Fig. 5-2.
The prepared coated nanometer gold FA-GNPs of folic acid of the present invention can carry out the imaging at body tumor CT.The model animal tumor model is all planted Cervical Tumor at the afterbody left and right sides of mice, treats that tumor is grown up to carry out about 1cm in body experiment, as shown in Figure 6.
At the FA-GNPs of a side tumor injection 200 μ L260mg Au/mL of nude mice, opposite side is injected 200 μ L PBS solution (see figure 7)s, carries out the CT scan imaging in the experiment.Fig. 7 (A～L) be nude mice from the to the end CT imaging of varying cross-section of tail, left and right directions and nude mice photo mirror image.Fig. 7 (there is the HepG2 tumor region of FA-GNPs at arrow indication place for injection among the D～F), as seen should the zone high-contrast, be as good as with skeleton brightness, and contralateral control group and soft tissue can't be distinguished.Both contrast the CT imaging that apparent FA-GNPs can provide for tumor high-contrast.
Claims (10)
1. the preparation method of the coated nanometer gold of a folic acid is characterized in that, may further comprise the steps:
1) take folic acid as coating agent, folic acid is dissolved in the solution that contains gold ion for the preparation of nanometer gold, and to regulate its pH is 7.0～7.5 that obtain mixed solution, the mol ratio of its Folic Acid and gold ion is 1:2～6;
2) add Reducing agent in mixed solution, then rapid stirring reacts at least 1h, natural cooling after reaction finishes, and unreacted part is removed in dialysis, obtains the coated nanometer gold of folic acid.
2. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that the described solution that contains gold ion for the preparation of nanometer gold is chlorauric acid solution.
3. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that, folic acid is water-soluble, and heated and stirred waits after folic acid dissolves fully, joins in the solution that contains gold ion again.
4. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that the concentration of described mixed solution Folic Acid is 0.08～0.24mmol/L, and the concentration of gold ion is 0.4～1.5mmol/L.
5. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that described Reducing agent is sodium borohydride, and the mol ratio of sodium borohydride and gold ion is 520:4～15.
6. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that, adds Reducing agent in mixed solution, rapid stirring reaction 2～3h then, and mixing speed is 1000～1500 rev/mins.
7. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that, its dialysis of described dialysis is dammed molecular weight greater than the material of 500 ~ 1000D, dialyses 6～12 hours.
8. the preparation method of the coated nanometer gold of folic acid as claimed in claim 1 is characterized in that the particle diameter of the nanometer gold that prepared folic acid is coated is 3～5nm, is in the 3.5%NaCl solution and 25000r/min is centrifugal all coagulation can not occur down in mass concentration.
9. the application of preparation method in the CT imaging molecular probe of preparation folacin receptor target tumor of the coated nanometer gold of folic acid claimed in claim 1.
10. the coated nanometer gold of the prepared folic acid of claim 1 is as the application of the CT imaging molecular probe of folacin receptor target tumor.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210528411.9A CN102989015B (en) | 2012-12-10 | 2012-12-10 | Preparation method of CT imaging molecular probe of folate receptor targeted tumor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210528411.9A CN102989015B (en) | 2012-12-10 | 2012-12-10 | Preparation method of CT imaging molecular probe of folate receptor targeted tumor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102989015A true CN102989015A (en) | 2013-03-27 |
| CN102989015B CN102989015B (en) | 2014-12-10 |
Family
ID=47918442
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210528411.9A Expired - Fee Related CN102989015B (en) | 2012-12-10 | 2012-12-10 | Preparation method of CT imaging molecular probe of folate receptor targeted tumor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102989015B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103627386A (en) * | 2013-12-04 | 2014-03-12 | 哈尔滨师范大学 | Preparation method for folic acid functionalized fluorogold nano-cluster of fluorescent probe |
| CN105920621A (en) * | 2016-06-21 | 2016-09-07 | 上海交通大学医学院附属瑞金医院 | Tumor targeted hypoxia CT imaging nanoprobe based on gold nanoparticles and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709517A (en) * | 2005-06-06 | 2005-12-21 | 中国人民解放军第二军医大学 | Magnetic resonance tumour target contrast media and preparing method thereof |
| CN102029401A (en) * | 2010-11-30 | 2011-04-27 | 厦门大学 | Synthesis method for folate receptor targeted type nano gold particles |
-
2012
- 2012-12-10 CN CN201210528411.9A patent/CN102989015B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709517A (en) * | 2005-06-06 | 2005-12-21 | 中国人民解放军第二军医大学 | Magnetic resonance tumour target contrast media and preparing method thereof |
| CN102029401A (en) * | 2010-11-30 | 2011-04-27 | 厦门大学 | Synthesis method for folate receptor targeted type nano gold particles |
Non-Patent Citations (2)
| Title |
|---|
| ALLEN C. TEMPLETON ET AL.，: "Monolayer-Protected Cluster Molecules", 《ACC. CHEM. RES.》 * |
| SHIAO-WEN TSAI ET AL.: "Surface-Modified Gold Nanoparticles with Folic Acid as Optical Probes for Cellular Imaging", 《SENSORS》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103627386A (en) * | 2013-12-04 | 2014-03-12 | 哈尔滨师范大学 | Preparation method for folic acid functionalized fluorogold nano-cluster of fluorescent probe |
| CN103627386B (en) * | 2013-12-04 | 2016-04-20 | 哈尔滨师范大学 | A kind of preparation method of fluorogold nano-cluster of fluorescent probe folic acid functionalization |
| CN105920621A (en) * | 2016-06-21 | 2016-09-07 | 上海交通大学医学院附属瑞金医院 | Tumor targeted hypoxia CT imaging nanoprobe based on gold nanoparticles and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102989015B (en) | 2014-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yang et al. | Albumin-bioinspired Gd: CuS nanotheranostic agent for in vivo photoacoustic/magnetic resonance imaging-guided tumor-targeted photothermal therapy | |
| Liu et al. | Nanoparticulate X-ray computed tomography contrast agents: from design validation to in vivo applications | |
| Li et al. | 99mTc-labeled multifunctional low-generation dendrimer-entrapped gold nanoparticles for targeted SPECT/CT dual-mode imaging of tumors | |
| Zheng et al. | Biodegradable silica‐based nanotheranostics for precise MRI/NIR‐II fluorescence imaging and self‐reinforcing antitumor therapy | |
| Chen et al. | Core–Shell Pd@ Au nanoplates as theranostic agents for in‐vivo photoacoustic imaging, ct imaging, and photothermal therapy | |
| Yang et al. | Renal clearance and degradation of glutathione-coated copper nanoparticles | |
| Yang et al. | Rod-shape MSN@ MoS2 nanoplatform for FL/MSOT/CT imaging-guided photothermal and photodynamic therapy | |
| Yang et al. | Long-term in vivo biodistribution and toxicity of Gd (OH) 3 nanorods | |
| Gao et al. | Protein‐modified CuS nanotriangles: A potential multimodal nanoplatform for in vivo tumor photoacoustic/magnetic resonance dual‐modal imaging | |
| Shi et al. | Chelator-free labeling of layered double hydroxide nanoparticles for in vivo PET imaging | |
| Fan et al. | Design and Biomedical Applications of Poly (amidoamine)‐Dendrimer‐Based Hybrid Nanoarchitectures | |
| Zhu et al. | Synthesis of heterodimer radionuclide nanoparticles for magnetic resonance and single-photon emission computed tomography dual-modality imaging | |
| Guo et al. | Intelligent nanoenzyme for T1-weighted MRI guided theranostic applications | |
| Reyes-Esparza et al. | Synthesis, characterization and biocompatibility of cadmium sulfide nanoparticles capped with dextrin for in vivo and in vitro imaging application | |
| Liu et al. | Anti‐Biofouling Polymer‐Decorated Lutetium‐Based Nanoparticulate Contrast Agents for In Vivo High‐Resolution Trimodal Imaging | |
| Wang et al. | Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex shell for upconversion fluorescent and magnetic resonance dual-modality imaging | |
| Jin et al. | Facile synthesis of gold nanorods/hydrogels core/shell nanospheres for pH and near-infrared-light induced release of 5-fluorouracil and chemo-photothermal therapy | |
| Chu et al. | Ultrasmall Au–Ag alloy nanoparticles: protein-directed synthesis, biocompatibility, and X-ray computed tomography imaging | |
| Zhao et al. | Lanthanide europium MOF nanocomposite as the theranostic nanoplatform for microwave thermo-chemotherapy and fluorescence imaging | |
| Zhu et al. | 99mTc-Labeled polyethylenimine-entrapped gold nanoparticles with pH-responsive charge conversion property for enhanced dual mode SPECT/CT imaging of cancer cells | |
| Tangthong et al. | Water-soluble chitosan conjugated DOTA-bombesin peptide capped gold nanoparticles as a targeted therapeutic agent for prostate cancer | |
| CN103288061A (en) | Bismuth selenide nanometer material, preparation method and applications thereof | |
| CN105148281A (en) | Method for preparing core-shell type polysaccharide gum location targeting carrier material | |
| CN102989015B (en) | Preparation method of CT imaging molecular probe of folate receptor targeted tumor | |
| Gao et al. | Nanomagnetic liposome-encapsulated parthenolide and indocyanine green for targeting and chemo-photothermal antitumor therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141210 Termination date: 20211210 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |