CN109692335B - Nanoparticles targeting systemic multistage lymph nodes, preparation method and application - Google Patents
Nanoparticles targeting systemic multistage lymph nodes, preparation method and application Download PDFInfo
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Abstract
The invention discloses a nano-particle targeting a systemic multistage lymph node, and relates to the technical field of bioscience and drug carriers. The invention also discloses a preparation method of the nanoparticle targeting the systemic multistage lymph nodes, and the preparation process is simple. The invention also discloses an application of the nano-particles for targeting the multistage lymph nodes of the whole body, and the nano-particles are applied to preparing a medicament which carries two or more of a CT contrast agent, a fluorescent substance and a PET contrast agent for targeting the multistage lymph nodes of the whole body. The invention also discloses another nano-particle for targeting the systemic multilevel lymph nodes, which also comprises a DMPE-DTPA-Gd phospholipid derivative. The nanoparticles can be used to prepare a medicament carrying two or more of a CT contrast agent, a fluorescent substance, an MRI contrast agent, and a PET contrast agent targeted to the systemic multistage lymph nodes.
Description
Technical Field
The invention relates to the technical field of bioscience and drug carriers, in particular to a nanoparticle targeting a systemic multistage lymph node, a preparation method and application.
Background
The lymphatic vasculature, including lymph nodes and the lymphatic vessels between lymph nodes, plays an important role in the human body. The system has strong permeability and transport capacity, and is mainly responsible for the collection of antigen substances under normal conditions and the promotion of adaptive immune response, including the promotion of the proliferation of antigen-specific T lymphocytes and the production of antibodies. However, in the case of tumor metastasis, the lymph node becomes one of the tissues in which metastatic tumor cells are most likely to aggregate due to the above characteristics. The visual analysis of the lymph nodes with metastasis in different periods is not only an important index of the tumor stage but also an important index of the prognosis of patients. The X-ray Computed Tomography (CT) technique has been widely used for tumor detection with the advantages of higher spatial resolution and no limitation of imaging depth, but has lower detection sensitivity. Fluorescence imaging has high detection sensitivity, so that the detection of metastatic foci or sentinel lymph nodes in the clinical operation process is widely applied, but the penetration depth is limited, and single fluorescence imaging still has a plurality of limitations in the detection of tumors and metastatic foci. PET (positron emission tomography) is also a commonly used imaging technique, which has the advantage of higher imaging sensitivity, but lower spatial resolution.
According to the current report, the particle size of about 20-60nm is most beneficial to the migration of the nano-particles in the lymphatic vasculature. However, there is a lack of subcutaneous injection of nanocarriers that can simultaneously target multiple lymph nodes throughout the body (the popliteal lymph nodes, the caudate lymph node, the lumbar lymph node, the adrenal lymph node, the mesenteric lymph node, the inguinal lymph node, the axillary lymph node, the thoracic duct, and the like), whether in human clinical applications or in animal model experiments. Meanwhile, no multi-modal nanoparticle capable of simultaneously carrying two or more of a fluorescent substance, a CT contrast agent, and a PET contrast agent has been found.
Therefore, a nano-carrier which effectively targets the multistage lymph nodes of the whole body is needed, and can simultaneously carry two or more of a fluorescent substance, a CT contrast agent and a PET contrast agent to target the multistage lymph nodes of the whole body, so as to realize multi-modal contrast imaging analysis of the multistage lymph nodes of the whole body and improve the sensitivity and accuracy of detection of a lymphatic system.
Meanwhile, MRI (magnetic resonance imaging) has high imaging contrast and resolution, but dark part contrast generated by single-mode MRI imaging cannot be distinguished from normal dark parts of a body sometimes. Fluorescence, CT and MRI three-modality contrast imaging, and even fluorescence, CT, PET and MRI four-modality contrast imaging are sometimes required in the clinic. Therefore, a need still exists for a nanocarrier that can effectively target a multistage lymph node of the whole body, and can simultaneously carry two or more of a fluorescent substance, a CT contrast agent, a PET contrast agent and an MRI contrast agent to target the multistage lymph node of the whole body, so as to realize multi-modal contrast imaging analysis of the multistage lymph node of the whole body.
Disclosure of Invention
Aiming at the defects in the prior art, the invention aims to provide the nanoparticles for targeting the multistage lymph nodes of the whole body, which can simultaneously carry two or more of fluorescent substances, CT contrast agents and PET contrast agents to target the multistage lymph nodes of the whole body, and realize the multi-modal contrast imaging analysis of the multistage lymph nodes of the whole body.
In order to achieve the purpose, the invention adopts the technical scheme that: the nanoparticles include phospholipids, iodonium oil, an optical probe, and an alpha-helical polypeptide.
On the basis of the scheme, the phospholipid is one or more of DMPC, MHPC, DMPE and DSPE-PEG 2000.
On the basis of the scheme, the optical probe is a water-soluble optical probe or a fat-soluble optical probe.
On the basis of the scheme, the water-soluble optical probe is ICG.
On the basis of the scheme, the alpha-helix polypeptide sequence is FAEKFKEAVKDYFAKFWD or a polypeptide containing FAEKFKEAVKDYFAKFWD sequence.
Compared with the prior art, the invention has the advantages that:
the nano-particles targeting the multistage lymph nodes of the whole body have excellent physical and chemical properties, uniform particle size, good dispersibility and no aggregation phenomenon; the raw materials used are phospholipid, iodized oil, optical probe and alpha-helical polypeptide, and the raw materials are respectively used in clinical or clinical tests and have good biocompatibility. The nano-particles can simultaneously carry two or more of fluorescent substances, CT contrast agents and PET contrast agents to target the multistage lymph nodes of the whole body, and multi-modal contrast imaging analysis of the multistage lymph nodes of the whole body is realized.
The invention also aims to provide a preparation method of the nano-particles targeting the multistage lymph nodes of the whole body, which is used for synthesizing the nano-particles capable of simultaneously carrying a fluorescent substance and two or more of a CT contrast agent and a PET contrast agent.
In order to achieve the purpose, the invention adopts the technical scheme that: a method for preparing nanoparticles targeted to multiple lymph nodes throughout the body, comprising the steps of:
a1, dissolving the phospholipid and the iodized oil in a mixed solution of chloroform and methanol;
a2, placing the mixed solution obtained in the step A1 in a round-bottom flask, and vacuumizing and drying the organic solvent in the mixed solution;
a3, placing the round-bottom flask treated in the step A2 in water bath at the temperature of between 40 and 60 ℃ to remove residual organic solvent;
a4, adding double distilled water to a round-bottom flask and filling with N2Carrying out vortex treatment after sealing to prepare hydrated nano particles;
a5, carrying out ultrasonic treatment on the hydrated nano particles;
a6, mixing and sealing the nano-particles after ultrasonic treatment with the dissolved alpha-helical polypeptide and the optical probe solution;
a7, and purifying the solution treated in the step A6 by using FPLC, dialysis or centrifugal separation method to obtain the final product.
Compared with the prior art, the invention has the advantages that:
the preparation method of the nanoparticle targeting the systemic multistage lymph nodes provided by the invention is simple in preparation process and convenient for large-scale production.
The invention also aims to provide application of the nanoparticles for targeting the multistage lymph nodes of the whole body, and the multimodal imaging analysis of the multistage lymph nodes of the whole body is realized.
In order to achieve the purpose, the invention adopts the technical scheme that: the nano-particles are applied to preparation of medicaments carrying two or more of CT contrast agents, fluorescent substances and PET contrast agents to target the multistage lymph nodes of the whole body.
Compared with the prior art, the invention has the advantages that:
the medicament prepared by the nano-particles can carry two or more kinds of CT contrast agents, fluorescent substances and PET contrast agents to target the multistage lymph nodes of the whole body, has the long-distance deep multistage lymph node targeting contrast capability, is suitable for visually detecting the superficial and deep lymph nodes of an organism, and realizes the multi-modal contrast imaging analysis of the multistage lymph nodes of the whole body.
The invention also aims to provide another nanoparticle targeting the multistage lymph nodes of the whole body, which can simultaneously carry two or more of fluorescent substances, CT contrast agents, PET contrast agents and MRI contrast agents to target the multistage lymph nodes of the whole body, and realize multi-modal contrast imaging analysis on the multistage lymph nodes of the whole body.
In order to achieve the purpose, the invention adopts the technical scheme that: the nanoparticle comprises phospholipid, iodized oil, an optical probe and alpha-helical polypeptide, and also comprises a DMPE-DTPA-Gd phospholipid derivative.
Compared with the prior art, the invention has the advantages that:
the nano-particles can carry CT contrast agents, fluorescent substances and PET contrast agents to target multi-level lymph nodes of the whole body, can also carry MRI contrast agents to target the multi-level lymph nodes of the whole body, and have more diversified multi-level lymph node targeting contrast capabilities.
The invention also aims to provide application of another nanoparticle targeting the multistage lymph nodes of the whole body, which can simultaneously carry two or more of fluorescent substances, CT contrast agents, PET contrast agents and MRI contrast agents to the multistage lymph nodes of the whole body, and realize multi-modal contrast imaging analysis on the multistage lymph nodes of the whole body.
In order to achieve the purpose, the invention adopts the technical scheme that: the nanoparticles are used for preparing medicaments carrying two or more of CT contrast agents, fluorescent substances, MRI contrast agents and PET contrast agents to target the multistage lymph nodes of the whole body.
Compared with the prior art, the invention has the advantages that:
the medicament prepared by the nano particles can carry CT contrast agents and fluorescent substances to target multistage lymph nodes, and can also carry MRI contrast agents to target multistage lymph nodes. Therefore, the nano-particles can be used for preparing a medicament which carries two or more of a CT contrast agent, a fluorescent substance, an MRI contrast agent and a PET contrast agent to target multistage lymph nodes and has more diversified multistage lymph node targeting contrast capability.
Drawings
FIG. 1 is a schematic electron microscope of nanoparticles in an application of nanoparticles targeting the systemic multiple lymph nodes in example 1 of the present invention;
FIG. 2 is a graph showing the distribution of the particle size of nanoparticles in the application of nanoparticles targeting the multistage lymph nodes throughout the body in example 1 of the present invention;
FIG. 3 is a CT image and a fluorescence image of the detection of the targeted contrast effect of the nanoparticles on the multiple lymph nodes in example 4 of the present invention;
FIG. 4 is a schematic diagram of bimodal imaging of sentinel nodes of in situ breast cancer in example 5 of the present invention;
FIG. 5 is a schematic structural diagram of nanoparticles that can be used for multi-modality imaging contrast of CT/fluorescence, CT/MRI/fluorescence, CT/PET// MRI/fluorescence in the embodiment of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings and examples.
Example 1: nanoparticles targeting systemic multistage lymph nodes
The embodiment of the invention provides a nanoparticle targeting to systemic multistage lymph nodes, and as shown in fig. 5, the nanoparticle comprises phospholipid, iodized oil, an optical probe and alpha-helical polypeptide. The phospholipid is one or more of DMPC, MHPC, DMPE and DSPE-PEG 2000. The optical probe is a water-soluble optical probe or a fat-soluble optical probe. The water-soluble optical probe was ICG. The alpha-helical polypeptide sequence is FAEKFKEAVKDYFAKFWD or a polypeptide comprising the sequence FAEKFKEAVKDYFAKFWD. The amino acid sequence of the alpha helix polypeptide is shown as SEQ ID NO.1 in the sequence table. Referring to fig. 1, the schematic electron microscope of the nanoparticles shows that the nanoparticles have uniform particle size distribution. Referring to FIG. 2, the particle size distribution of the nanoparticles is shown to be 60. + -. 1.75 nm.
Example 2: preparing nanoparticles wrapping water-soluble optical probe ICG and iodized oil
The embodiment of the invention provides a preparation method of nanoparticles targeting a systemic multistage lymph node, which comprises the following steps:
a1, dissolving DMPC, MHPC, DMPE, DSPE-PEG2000 and iodized oil in a chloroform-methanol mixed solution (volume ratio is 2: 1); wherein the mass portions of DMPC are 6-8, MHPC is 1.5-2, DMPE is 2.5-3.5, DSPE-PEG2000 is 2.5-3.5, and iodized oil is 30-35.
A2, vacuum drying
Placing the mixed solution obtained in the step A1 in a round-bottom flask, and carrying out water bath ultrasound for 30 s; then, pumping the organic solvent by using a vacuum pump, and stirring by using a magnetic stirrer while vacuumizing; the drying time is 2 hours until the organic solvent is completely extracted;
a3, water bath
Placing the round-bottom flask extracted in the step A2 in water at 50 ℃, continuing the water bath for 20min, and removing residual organic solvent through the step;
a4, hydration
Will ddH2O (temperature 60 ℃ C.) was added to the round bottom flask in A3, and N was charged2Sealing the bottle mouth with a sealing film, and fully whirling on a whirling vibration instrument; it can be seen that the thin layer remaining on the wall of the bottle is well dispersed in the solution;
a5, ultrasound
The particle size ratio of the hydrated nano particles is larger, the particle size of the nano particles is reduced by an ultrasonic method, the nano particles in the step A4 are placed in an ultrasonic instrument for ultrasonic treatment, the ultrasonic temperature is 45 ℃, and the ultrasonic time is 20 min;
a6, addition of ICG and polypeptide
Add ddH containing ICG dye to the tube in step A52Mixing the solution O and the solution O uniformly; addition of ddH containing alpha-helical polypeptide2O solution, wherein the weight portion of the O solution,2-4 parts of alpha helical polypeptide and 0.25-0.3 part of ICG dye, mixing uniformly, sealing, and standing overnight at 4 ℃;
a7, purifying by using fast protein separation system (FPLC), dialysis or centrifugation.
For example, the solution in the nanoparticles in step a6 is replaced by PBS by a concentration centrifuge tube, and after further concentration, the solution is purified by using a fast protein separation system (FPLC), and the effective solution is collected and concentrated, and the concentration of the polypeptide is detected for use.
Example 3: preparing nano-particles wrapping fat-soluble optical probe DiR-BOA and iodized oil
Referring to example 2, except that DiR-BOA is added to a1, wherein the alpha helical polypeptide is 2-4 parts by mass and the DiR-BOA is 0.24-0.3 part by mass, the DiR-BOA is wrapped in the nanoparticles through the hydrophobic core of the nanoparticles, and the nanoparticles are concentrated and purified in a7 for use.
Example 4: multi-stage targeted validation of nanoparticles to the systemic lymphatic system
The nanoparticles in example 1 were injected into mice, CT and fluorescence imaging were performed at different time points, and the targeted contrast effect of the nanoparticles on multiple lymph nodes was examined.
1) Mouse preparation
C57BL/6 mice were depilated in the area between the forelimb and the tail root;
2) nanoparticle injection
Anesthetizing the mouse in the step 1), inserting a needle from the middle part of the second toe of the dorsum of the foot of the mouse by using an insulin syringe, slowly pushing and placing the middle part of the dorsum of the foot, then starting to inject the nanoparticles with the volume of 50 mu L, wherein the speed of pushing the needle is slow, and after the injection is finished, the syringe is continuously kept in the original position for 5-10min to avoid the nanoparticles from leaking out, and after the injection is finished, lightly clamping the injection part by using tweezers for 10 s;
3) CT and fluorescence imaging
Carrying out CT and integral fluorescence imaging on the mouse injected with the nanoparticles;
4) data processing
Processing of fluorescence images and three-dimensional reconstruction of CT results.
Referring to FIG. 3, structures 1-8 in the figure are the popliteal lymph node, the caudal lymph node, the lumbar lymph node, the renal lymph node, the mesenteric lymph node, the inguinal lymph node, the axillary lymph node, and the thoracic duct, respectively.
From the imaging results, it can be seen that the lymph nodes that the nanoparticles can reach are: the lymph nodes in the leg elbow, the ischial lymph nodes, the inguinal lymph nodes, the adrenal lymph nodes, the mesenteric lymph nodes, the axillary lymph nodes and the inguinal lymph nodes.
Example 5: application of nano-particles in CT/fluorescence bimodal radiography of sentinel lymph node of mouse breast cancer
1) Model preparation
Taking one FVB/N-Tg (MMTVneu)202Mul/J tumor-bearing female mouse with the age of 40 weeks, and carrying out unhairing treatment on a required imaging part;
2) intratumoral injection
Sucking 50 μ L of the nanoparticles of example 1 with an insulin syringe, inserting the needle from the middle part of the tumor, then slowly injecting, and after the injection is finished, keeping the needle in the tumor for 10min to prevent the injected nanoparticles from overflowing;
3) CT and fluorescence imaging
And (3) carrying out CT and fluorescence imaging detection on the tumor and the sentinel lymph node 6h after 2) is finished, wherein the imaging result shows that in a spontaneous breast cancer model, as shown in figure 4, the nano particles can carry a CT contrast agent and a fluorescent substance to reach the sentinel lymph node from the tumor part and have an obvious imaging effect.
Example 6: nanoparticles for CT, fluorescence and PET three-modality imaging contrast
Referring to FIG. 5, the nanoparticles of example 1 were made radioactive using the lactose-amino acid reaction18F-labelling, radioactivity18F will label the alpha-helical polypeptide (R4F) of the nanoparticle to form a polypeptide with radioactivity18F-labeled nanoparticles, which can carry a PET contrast agent. Therefore, the nanoparticles of the present embodiment are applied to the preparation of a medicament which can not only target multiple lymph nodes with a CT contrast agent and a fluorescent substance, but also carry the CT contrast agent and the fluorescent substanceCan simultaneously carry CT contrast agent, fluorescent substance and PET contrast agent to target the whole body and multilevel lymph nodes.
Example 7: nanoparticles for CT, fluorescence and MRI three-modality imaging contrast
Referring to fig. 5, the nanoparticle comprises phospholipid, iodized oil, an optical probe and an alpha-helical polypeptide, and the nanoparticle further comprises DMPE-DTPA-Gd phospholipid derivative. Wherein the phospholipid is one or more of DMPC, MHPC, DMPE and DSPE-PEG 2000. The optical probe is a water-soluble optical probe or a fat-soluble optical probe. The water-soluble optical probe was ICG. The alpha-helical polypeptide sequence is FAEKFKEAVKDYFAKFWD or a polypeptide comprising the sequence FAEKFKEAVKDYFAKFWD. The amino acid sequence of the alpha helix polypeptide is shown as SEQ ID NO.1 in the sequence table.
Example 8: preparation method of CT, fluorescence and MRI (magnetic resonance imaging) trimodal nanoparticles
The preparation method of the nanoparticles in example 7 includes the following steps:
b1, mixing DMPE-DTPA and GdCl3·6H2O is coupled through chemical bonds to form DMPE-DTPA-Gd phospholipid derivatives; dissolving DMPC, MHPC, DMPE, DSPE-PEG2000, iodized oil and DMPE-DTPA-Gd phospholipid derivative in a mixed solution (volume ratio is 2:1) of chloroform and methanol; wherein the weight portions of the DMPC, the MHPC, the DMPE, the DSPE-PEG2000 and the DMPE-DTPA-Gd are 6-8, 1.5-2, 0.5-1, 2.5-3.5 and 30-35 respectively.
B2, vacuum drying
Placing the mixed solution obtained in the step B1 in a round-bottom flask, and carrying out water bath ultrasound for 30 s; then, pumping the organic solvent by using a vacuum pump, and stirring by using a magnetic stirrer while vacuumizing; the drying time is 2 hours until the organic solvent is completely extracted;
b3, water bath
Placing the round-bottom flask extracted in the step B2 in water at 50 ℃, continuing the water bath for 20min, and removing residual organic solvent through the step;
b4, hydration
Will ddH2O (temperature 60 ℃) was added to the round bottom flask in B3, charged with N2Sealing the bottle mouth with a sealing film in a vortexFully whirling on a vibration meter; it can be seen that the thin layer remaining on the wall of the bottle is well dispersed in the solution;
b5, ultrasound
The particle size ratio of the hydrated nano particles is larger, the particle size of the nano particles is reduced by an ultrasonic method, the nano particles in the step B4 are placed in an ultrasonic instrument for ultrasonic treatment, the ultrasonic temperature is 45 ℃, and the ultrasonic time is 20 min;
b6 addition of ICG and polypeptide
Add ddH containing ICG dye to the tube in step B52Mixing the solution O and the solution O uniformly; addition of ddH containing alpha-helical polypeptide2O solution, wherein the alpha helical polypeptide accounts for 2-4 parts by mass, the ICG dye accounts for 0.25-0.3 part by mass, the alpha helical polypeptide and the ICG dye are uniformly mixed and sealed, and the mixture is placed at 4 ℃ overnight;
b7, purification using Fast Protein Liquid Chromatography (FPLC), dialysis or centrifugation.
For example, the solution in the nanoparticles in step B6 is replaced by PBS by a concentration centrifuge tube, and after further concentration, purification is performed by Fast Protein Liquid Chromatography (FPLC), and the effective solution is collected and concentrated, and the concentration of the polypeptide is detected for use.
Example 9: nanoparticles for CT, fluorescence and MRI three-modality imaging contrast
The nanoparticles prepared using the method of example 8, as shown in fig. 5, can carry an MRI contrast agent. Therefore, the nano-particles are applied to preparing a medicament which can not only carry a CT contrast agent and a fluorescent substance to target multistage lymph nodes, but also simultaneously carry the CT contrast agent, the fluorescent substance and an MRI contrast agent to target the multistage lymph nodes.
Example 10: nanoparticles for CT, fluorescence, MRI and PET four-modality imaging contrast
The nanoparticles prepared using the method of example 8, as shown in fig. 5, can carry an MRI contrast agent. Nanoparticles synthesized by the method of example 8 were made radioactive by the lactose-amino acid reaction18F-labelling, radioactivity18F will label the alpha-helical polypeptide (R4F) of the nanoparticle to form a polypeptide with radioactivity18F-labeled nanoparticles so that the nanoparticles can carryA PET contrast agent. Therefore, the nanoparticles of the present embodiment may be used to prepare a pharmaceutical agent that may target multiple lymph nodes with two or more of CT contrast agents, fluorescent substances, MRI contrast agents, and PET contrast agents, with more diversified multiple lymph node targeting contrast capabilities.
Sequence listing
<110> university of science and technology in Huazhong
EZHOU INSTITUTE OF INDUSTRIAL TECHNOLOGY HUAZHONG University OF SCIENCE AND TECHNOLOGY
<120> nanoparticle targeting whole-body multistage lymph nodes, preparation method and application
<160> 1
<170> SIPOSequenceListing 1.0
<210> 1
<211> 18
<212> PRT
<213> Artificial Sequence (Artificial Sequence)
<400> 1
Phe Ala Glu Lys Phe Lys Glu Ala Val Lys Asp Tyr Phe Ala Lys Phe
1 5 10 15
Trp Asp
Claims (5)
1. A nanoparticle targeted to multiple lymph nodes throughout the body, comprising: the nano-particles comprise phospholipid, 30-35 parts of iodized oil, an optical probe and alpha-helical polypeptide; the phospholipid is 6-8 parts of DMPC, 1.5-2 parts of MHPC, 2.5-3.5 parts of DMPE and 2.5-3.5 parts of DSPE-PEG 2000; the optical probe is a water-soluble optical probe ICG or a fat-soluble optical probe DiR-BOA; the alpha-helical polypeptide sequence is FAEKFKEAVKDYFAKFWD.
2. A method of preparing a nanoparticle targeting a systemic multistage lymph node according to claim 1, comprising:
a1, dissolving the phospholipid and the iodized oil in a mixed solution of chloroform and methanol;
a2, placing the mixed solution obtained in the step A1 in a round-bottom flask, and vacuumizing and drying the organic solvent in the mixed solution;
a3, placing the round-bottom flask treated in the step A2 in water bath at the temperature of between 40 and 60 ℃ to remove residual organic solvent;
a4, adding double distilled water to a round-bottom flask and filling with N2Carrying out vortex treatment after sealing to prepare hydrated nano particles;
a5, carrying out ultrasonic treatment on the hydrated nano particles;
a6, mixing and sealing the nano-particles after ultrasonic treatment with the dissolved alpha-helical polypeptide and the optical probe solution;
a7, purifying the solution treated in the step A6 by using a method of rapid protein liquid chromatography, dialysis or centrifugal separation to obtain a final product.
3. Use of a nanoparticle according to claim 1 to target multiple lymph nodes throughout the body, wherein: the nano-particles are applied to preparation of medicaments carrying two or more of CT contrast agents, fluorescent substances and PET contrast agents to target the multistage lymph nodes of the whole body.
4. A nanoparticle targeted to multiple lymph nodes throughout the body, comprising: the nano-particles comprise 6-8 parts of DMPC, 1.5-2 parts of MHPC, 0.5-1 part of DMPE, 2.5-3.5 parts of DSPE-PEG2000, 2.5-3.5 parts of DMPE-DTPA-Gd, 30-35 parts of iodized oil, an optical probe and alpha-helical polypeptide, wherein the optical probe is a water-soluble optical probe ICG or a fat-soluble optical probe DiR-BOA; the alpha-helical polypeptide sequence is FAEKFKEAVKDYFAKFWD.
5. Use of a nanoparticle according to claim 4 to target multiple lymph nodes throughout the body, wherein: the nanoparticles are used for preparing medicaments carrying two or more of CT contrast agents, fluorescent substances, MRI contrast agents and PET contrast agents to target the multistage lymph nodes of the whole body.
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| CT/FMT dual-model imaging of breast cancer based on peptide-lipid nanoparticles;Guoqiang Xu et al.;《Proc. of SPIE》;20160315;第9709卷;第97090S页 * |
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