CN105412950B - With MRI/SPECT bimodal image cancer target multifunctional nano probes and preparation and application - Google Patents
With MRI/SPECT bimodal image cancer target multifunctional nano probes and preparation and application Download PDFInfo
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Abstract
The present invention relates to one kind to have MRI/SPECT bimodal image cancer target multifunctional nano probes and its preparation and application, and nano-probe is included by Fe@Fe3O4Nano-particle is coupled at Fe@Fe3O4The MNPs DSPE PEG RGD nano-probes of liposome DSPE PEG RGD and liposome DSPE the PEG compositions on nano-particle surface layer, can also mark radionuclide I on MNPs DSPE PEG RGD nano-probes125, composition MNPs DSPE PEG RGD I125Nano-probe；It adds in Fe@Fe by the way that DSPE PEG RGD and DSPE PEG are dissolved in organic solvent3O4Nano-particle solution is uniformly mixed, and obtains MNPs DSPE PEG RGD nano-probes, then mark I with chloramine-t method125To get to MNPs DSPE PEG RGD I125Nano-probe.Nano-probe MNPs DSPE PEG RGD obtained are used for human glioma MRI magnetic resonance imagings, MNPs DSPE PEG RGD I125Nano-probe images for SPECT.Compared with prior art, the present invention has many advantages, such as that targeting is strong, and different kinds of molecules image probe can be carried out on same molecule.
Description
Technical field
The present invention relates to a kind of multifunctional nano probes, more particularly, to one kind there is MRI/SPECT bimodal images to swell
Knurl targets multifunctional nano probe and its preparation and application.
Background technology
Molecular imaging (molecular imaging, MI) is proposed earliest by the Weissleder of Harvard University, is used at present
Include CT, MRI, US, PET, SPECT and optical imagery etc. in the technology of molecular imaging research.But without a kind of single mode
Imaging can provide all necessary information for medical diagnosis on disease and treatment.In view of the advantage and disadvantage of each single mode imaging itself, closely
Nian Lai, bis- (more) mode molecular imagings are increasingly becoming the hot spot of research and development, while have also driven opening for bis- (more) mode molecular probes
Hair structure.Nanometer technology provides platform to build ideal bis- (more) mode molecular probes, while collects quantitative, noninvasive and targeting
The research treated in the bimodal probe of one has also achieved impressive progress.SPECT and MRI conjunctive uses are the morning of tumour
Phase diagnoses and the improvement for the treatment of plan provides important tool.With deepening continuously for molecular imaging, it is believed that SPECT/MRI
The application that bimodal is imaged in disease will surmount PET/MRI because PET inspection fees are expensive, can not extensive use, and
SPECT is not only moderate, and the tracer half-life period for being used to mark is considerably longer than tracer used in PET, for probe in vivo
It finds target and provides the sufficient time.
With the continuous development of nanosecond science and technology and nanosecond medical science, using nano material as the diagnosis and treatment Integral of pharmaceutical carrier
Metric system agent integrated is received what targeting functional group, multi-mode molecular image probe, multimachine conjoint therapy were integrated in one
Rice compound system, completely new diagnosis and treatment medical procedures are provided for cancer, therefore, the cancer of targeting multi-mode molecular image guidance
Combination therapy and dynamic examination of curative effect, have become the hot research direction of nanosecond medical science, and achieve major progress.Nanometer material
Material and the diagnosing tumor treatment technology in minute manufacturing technical foundation, are expected to become the effective means for capturing tumour.
Chinese patent 201310425589.5 disclose a kind of novel bimodal cancer target nano-particle developer and
Preparation method, using the near-infrared core cross-linked polymeric micelles nano-particle (NIRF-CCPM) with excellent biology performance as
Polypeptide RGD (arginine-glycine-aspartic acid) with tumor-targeting and nano-particle are coupled by carrier, are obtained novel
Cancer target nano molecular image probe NIRF-CCPM-RGD, and with radionuclide111In is marked, and obtains111In-NIRF-CCPM-RGD.The carrier NIRF-CCPM of the patent poly- (three second of poly- (PEG- the acrylic acid)-b- of two kinds of precursors
Oxysilane base acrylate) and NIRF dyestuffs 3- (triethoxysilyl) propyl-Cy7 pass through collection polymer micella
Method, reaction step complexity and precursor raw material higher price.
Invention content
It is an object of the present invention to overcome the above-mentioned drawbacks of the prior art and provide one kind has MRI/SPECT
Bimodal image cancer target multifunctional nano probe and its preparation and application.
The purpose of the present invention can be achieved through the following technical solutions：
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4The liposome DSPE-PEG-RGD on nano-particle surface layer and liposome DSPE-PEG (phosphatidyls
Ethanol amine-polyethylene glycol) composition MNPs-DSPE-PEG-RGD nano-probes.RGD is the polypeptide (essence with tumor-targeting
Propylhomoserin-Gly-Asp).
A diameter of 12~13nm of the MNPs-DSPE-PEG-RGD nano-probes.
Label has I on the MNPs-DSPE-PEG-RGD nano-probes125, and form MNPs-DSPE-
PEG-RGD-I125Nano-probe.
The MNPs-DSPE-PEG-RGD-I125The radio chemistry of nano-probe is pure to be more than 95%.
A kind of preparation method with MRI/SPECT bimodal image cancer target multifunctional nano probes, including following
Step：DSPE-PEG-RGD and DSPE-PEG are dissolved in organic solvent, add in Fe@Fe3O4Nano-particle solution is uniformly mixed,
Organic solvent is removed, adds water, diafiltration, obtains MNPs-DSPE-PEG-RGD nano-probes.
DSPE-PEG-RGD, DSPE-PEG and Fe@Fe3O4The ratio between additive amount of nano-particle is (4~6)：(7~13)：
0.5。
The organic solvent be chloroform, the Fe@Fe3O4Nano-particle solution is 0.5~1.5mg/mL's of concentration
Fe@Fe3O4The ratio between nano-particle solution chloroformic solution, the additive amount of organic solvent, DSPE-PEG-RGD and water is 2mL：(4~6)
mg：(3~7) mL；
Uniformly mixed process conditions are：Incubator overnight at room temperature；
The technique for removing solvent is rotated for room temperature.
The process conditions of diafiltration can be：After 3500Da bag filters dialysis 48h, 0.22 μm of miillpore filter mistake is used
Filter.
A kind of preparation method with MRI/SPECT bimodal image cancer target multifunctional nano probes, further include with
Lower step：MNPs-DSPE-PEG-RGD aqueous solutions are configured, are charged with band I125Salt and chloramine-T aqueous solution, concussion carry out anti-
Should, it adds and lays particular stress on sulfite solution and terminate reaction, to get to MNPs-DSPE-PEG-RGD-I after ultrafiltration centrifugation125Nanometer
Probe.
The band I125Salt is NaI125, the weighting sulphite is Sodium Metabisulfite；
A concentration of 0.5~1.5mg/mL of the MNPs-DSPE-PEG-RGD aqueous solutions, the concentration of chloramine-T aqueous solution
For 3~5mg/mL, a concentration of 4~6mg/mL of sulfite solution is laid particular stress on；
MNPs-DSPE-PEG-RGD aqueous solutions, band I125Salt, chloramine-T aqueous solution and the addition for laying particular stress on sulfite solution
The ratio between amount is 1mL：(30~150) mg：(50~150) μ L：(150~250) μ L；
The time of concussion reaction is 4~8min；
Ultrafiltration centrifugation process conditions can be：Reaction solution is transferred in 10K ultra-filtration centrifuge tubes, add water through ultrafiltration from
Heart 4-5 times.
A kind of application with MRI/SPECT bimodal image cancer target multifunctional nano probes, the MNPs-
DSPE-PEG-RGD nano-probes are for the MRI magnetic resonance imagings of human glioma etc., the MNPs-DSPE-PEG-RGD-
I125Nano-probe images for SPECT.
The present invention is with high saturation magnetization magnetic Fe@Fe3O4Nano-particle (MNPs) is as carrier, surface
Containing substances such as oleyl amine, oleic acid, hydrophobicity is shown as.DSPE ends show as dredging in liposome DSPE-PEG-RGD and DSPE-PEG
It is aqueous, by two kinds of liposomes and Fe@Fe3O4Nano-particle mixes, and passes through hydrophobic Van der Waals interaction liposome DSPE-
PEG-RGD and DSPE-PEG is coupled at Fe@Fe3O4Nanoparticle surface obtains novel cancer target multifunctional nano molecule
Image probe MNPs-DSPE-PEG-RGD.Since liposome DSPE-PEG has very high biocompatibility, obtained nanometer is visited
Needle MNPs-DSPE-PEG-RGD has stronger biological phasic property, and can improve blood circulation time in vivo.Nanometer obtained
Probe MNPs-DSPE-PEG-RGD is by chloramine-t method, by free I125It is oxidized to iodine molecule I2 125, active iodine molecule I2 125
The hydrogen at hydroxyl ortho position on the phenyl ring on rgd peptide chain can be replaced, obtain that there is radioactive nano-probe MNPs-DSPE-
PEG-RGD-I125, chloramine-t method labeling effciency is high, reproducible, and reagent is cheap.Obtained nano-probe MNPs-DSPE-
PEG-RGD-I125Uniform particle diameter, saturation magnetization height, morphology controllable, good biocompatibility and Targeting Effect are good, in aqueous solution
In have well dispersibility and stability.Nano-probe MNPs-DSPE-PEG-RGD-I125It can be with tumor neogenetic blood vessels spy
The integrin alpha of different expressionvβ3With reference to, and then integrin alpha is accurately positioned by MRI/SPECT bimodals imaging methodsvβ3Height expression
Tissue, effectively reduce the damage of normal tissue cell in oncotherapy, reach the targeted molecular diagnostic imaging of tumour
Purpose.Further, since there is MNPs-DSPE-PEG-RGD nano-probes high saturation magnetization to be applicable to human glioma
MRI magnetic resonance imagings, MNPs-DSPE-PEG-RGD-I125Nano-probe is imaged suitable for SPECT, it is achieved thereby that same
The research of different kinds of molecules image probe is carried out on molecule.
Compared with prior art, the nano-probe MNPs-DSPE-PEG-RGD and MNPs-DSPE-PEG- that prepared by the present invention
RGD-I125Uniform particle diameter, saturation magnetization height, morphology controllable, good biocompatibility and Targeting Effect it is good, in aqueous solution
With good dispersibility and stability, preparation process is simple, and reaction condition is mild, and raw material sources are cheap and easy to get, obtained
Nano-probe MNPs-DSPE-PEG-RGD and MNPs-DSPE-PEG-RGD-I125Human glioma MRI magnetic is respectively suitable for be total to
Shake imaging and SPECT imaging, realize on same molecule carry out different kinds of molecules image probe research.
Description of the drawings
Fig. 1 is the nano-probe MNPs-DSPE-PEG-RGD-I of the present invention125Synthesis schematic diagram；
Fig. 2 is the Fe@Fe of the present invention3O4The TEM figures of nano-particle；
Fig. 3 is the Fe@Fe of the present invention3O4The XRD diagram of nano-particle；
Fig. 4 is the Fe@Fe of the present invention3O4The hysteresis loop figure of nano-particle；
Fig. 5 is the nano-probe MNPs-DSPE-PEG-RGD-I of the preparation of the present invention125Radio chemistry at 37 DEG C
Pure stability diagram；
Fig. 6 is the nano-probe MNPs-DSPE-PEG-RGD of the present invention in the BALB/C nude mouse tumors position that U87MG kinds are planted
MRI imagings figure under 7.0T；
Fig. 7 is the nano-probe MNPs-DSPE-PEG-RGD-I of the present invention125In the BALB/C nude mices of U87MG cell seedings
Internal SPECT imaging figures.
Specific embodiment
The present invention is described in detail with specific embodiment below in conjunction with the accompanying drawings.
In following embodiments, liposome DSPE-PEG-RGD's is prepared as liposome DSPE-PEG-NHS and RGD-NH2
Peptide carries out amide coupling reaction, obtains the liposome DSPE-PEG-RGD, the RGD-NH with Targeting Effect2Peptide is smart ammonia
Acid-Gly-Asp (Arg-Gly-Asp), specifically refer to document (Hong H, Shi J, Yang Y, Zhang Y,
Engle J,Nickles R,Wang X,Cai W.Cancer-Targeted Optical Imaging with
Fluorescent Zinc Oxide Nanowires.Nano Lett.2011,11,3744–3750.)。
Oil-soluble Fe@Fe3O4The preparation method of nano-particle (MNPs) can be used：Take 0.1g hexadecylamine hydrochlorides, 20mL 18
Alkene, 0.2mL oleyl amines, are added in three-neck flask, are warming up to 180 DEG C, are rapidly injected 0.7mL Fe (CO)5, holding 20~
30min adds in 0.3mL oleic acid, is cooled to room temperature, and exposure in air, stirs 1h, with n-hexane and chloroform mixed liquor (5:1)
Centrifugation 4~5 times, is dispersed in chloroform, the Fe@Fe of diluted concentration to 1mg/mL3O4Nano-particle.It can be with bibliography
(Lacroix LM,Huls NF,Ho D,Sun X,Cheng K,Sun S.Stable sigle-crystalline body
centered cubic Fe nanoparticles.Nano Lett2011；11:1641-5.).
By the TEM Electronic Speculum it can be seen from the figure thats in Fig. 2：The Fe@Fe prepared in the present invention3O4Nano-particle has apparent
Nucleocapsid；It can be seen that by the XRD spectrum of Fig. 3：The diffraction maximum of (110) (200) crystal face of crystalline state fe, ferroso-ferric oxide
Diffraction maximum do not see, be because of crystal region very little, peak broadens；As seen from Figure 4：Fe@Fe3O4Nano-particle saturation
Magnetic susceptibility reaches 100emu/g, has higher magnetism.
Embodiment 1
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, a diameter of 12~13nm of MNPs-DSPE-PEG-RGD nano-probes.
The above-mentioned preparation method with MRI/SPECT bimodal image cancer target multifunctional nano probes, including following
Step：5mg DSPE-PEG-RGD and 10mg DSPE-PEG is taken to be dissolved in 2mL chloroforms, adds in a concentration of 1mg/mL's of 0.5mL
Fe@Fe3O4Nano-particle solution chloroformic solution, incubator overnight, room temperature revolving remove chloroform, then in 80 DEG C of water-baths revolvings at room temperature
1min adds 5mL water, is dialysed two days with 3500Da bag filters, and using 0.22 μm of membrane filtration, the nanometer for obtaining 1mg/mL is visited
Needle MNPs-DSPE-PEG-RGD aqueous solutions are stored in spare in 4 DEG C of refrigerators.
Embodiment 2
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, a diameter of 12~13nm of MNPs-DSPE-PEG-RGD nano-probes.
The above-mentioned preparation method with MRI/SPECT bimodal image cancer target multifunctional nano probes, including following
Step：4mg DSPE-PEG-RGD and 7mg DSPE-PEG is taken to be dissolved in 2mL chloroforms, adds in a concentration of 0.5mg/mL's of 0.5mL
Fe@Fe3O4Nano-particle solution chloroformic solution, incubator overnight, room temperature revolving remove chloroform, add 3mL water, use at room temperature
3500Da bag filters are dialysed two days, using 0.22 μm of membrane filtration, obtain the nano-probe MNPs-DSPE-PEG-RGD of 1mg/mL
Aqueous solution is stored in spare in 4 DEG C of refrigerators.
Embodiment 3
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, a diameter of 12~13nm of MNPs-DSPE-PEG-RGD nano-probes.
The above-mentioned preparation method with MRI/SPECT bimodal image cancer target multifunctional nano probes, including following
Step：6mg DSPE-PEG-RGD and 13mg DSPE-PEG is taken to be dissolved in 2mL chloroforms, adds in a concentration of 1.5mg/mL's of 0.5mL
Fe@Fe3O4Nano-particle solution chloroformic solution, incubator overnight, room temperature revolving remove chloroform, add 7mL water, use at room temperature
3500Da bag filters are dialysed two days, using 0.22 μm of membrane filtration, obtain the nano-probe MNPs-DSPE-PEG-RGD of 1mg/mL
Aqueous solution is stored in spare in 4 DEG C of refrigerators.
Embodiment 4
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, and by marking radionuclide I on the nano-probe125, so as to form MNPs-
DSPE-PEG-RGD-I125Nano-probe, radio chemistry is pure to be more than the straight of 95%, MNPs-DSPE-PEG-RGD nano-probes
Diameter is 12~13nm.
Above-mentioned MNPs-DSPE-PEG-RGD-I125The preparation method of nano-probe is as follows：It is prepared in Example 1
1mg/mL nano-probe MNPs-DSPE-PEG-RGD aqueous solutions 0.1mL and NaI125(1.28mCi, 50mg) is placed in sample
Guan Zhong injects the chloramine-T aqueous solution of 10 a concentration of 4mg/mL of μ L, and after shaking 5min, a concentration of 5mg/mL of 20 μ L of injection lay particular stress on sub-
Sodium sulphate terminates reaction, and reaction solution is transferred in 10K ultra-filtration centrifuge tubes, water is added to be centrifuged 4-5 times through ultrafiltration, and be scattered in life
It manages in brine, obtains nano-probe MNPs-DSPE-PEG-RGD-I125(256 μ Ci), radio chemistry is pure to be more than 95%.
Fig. 5 shows the nano-probe MNPs-DSPE-PEG-RGD-I prepared in the present embodiment125The radioactivity at 37 DEG C
The pure stability diagram of chemistry.Radioactivity of the nano-probe in physiological saline and 10% 1640 culture medium of serum potassium after 14 days
Chemistry is pure to be more than 85%, this shows that the biological stability of nano-probe made from the present embodiment is good.
Embodiment 5
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, and by marking radionuclide I on the nano-probe125, so as to form MNPs-
DSPE-PEG-RGD-I125Nano-probe, radio chemistry is pure to be more than the straight of 95%, MNPs-DSPE-PEG-RGD nano-probes
Diameter is 12~13nm.
Above-mentioned MNPs-DSPE-PEG-RGD-I125The preparation method of nano-probe is as follows：It is prepared in Example 1
1mg/mL nano-probe MNPs-DSPE-PEG-RGD aqueous solutions 0.1mL and NaI125(1.06mCi, 40mg) is placed in sample
Guan Zhong injects the chloramine-T aqueous solution of 5 a concentration of 3mg/mL of μ L, and after shaking 4min, a concentration of 4mg/mL of 15 μ L of injection lay particular stress on sub-
Sodium sulphate terminates reaction, and reaction solution is transferred in 10K ultra-filtration centrifuge tubes, water is added to be centrifuged 4-5 times through ultrafiltration, and be scattered in life
It manages in brine, obtains nano-probe MNPs-DSPE-PEG-RGD-I125, radio chemistry is pure to be more than 95%.
Embodiment 6
One kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, including by Fe@Fe3O4Nanoparticle
Sub (MNPs), Fe@Fe are coupled at3O4Liposome DSPE-PEG-RGD and liposome the DSPE-PEG composition on nano-particle surface layer
MNPs-DSPE-PEG-RGD nano-probes, and by marking radionuclide I on the nano-probe125, so as to form MNPs-
DSPE-PEG-RGD-I125Nano-probe, radio chemistry is pure to be more than the straight of 95%, MNPs-DSPE-PEG-RGD nano-probes
Diameter is 12~13nm.
Above-mentioned MNPs-DSPE-PEG-RGD-I125The preparation method of nano-probe is as follows：It is prepared in Example 1
1mg/mL nano-probe MNPs-DSPE-PEG-RGD aqueous solutions 0.1mL and NaI125(0.98mCi, 30mg) is placed in sample
Guan Zhong injects the chloramine-T aqueous solution of 15 a concentration of 5mg/mL of μ L, and after shaking 8min, a concentration of 6mg/mL of 25 μ L of injection lay particular stress on sub-
Sodium sulphate terminates reaction, and reaction solution is transferred in 10K ultra-filtration centrifuge tubes, water is added to be centrifuged 4-5 times through ultrafiltration, and be scattered in life
It manages in brine, obtains nano-probe MNPs-DSPE-PEG-RGD-I125, radio chemistry is pure to be more than 95%.
Embodiment 7
Take the nano-probe MNPs-DSPE-PEG-RGD aqueous solutions being prepared in 0.1mL embodiments 1 and NaI125
(2.47mCi, 60mg) adds in a concentration of 4mg/mL chloramine-Ts of 10 μ L as in sample cell, after shaking 5min, adds in 20 μ L concentration
It terminates and reacts for 5mg/mL Sodium Metabisulfites, reaction solution is transferred in 10K ultra-filtration centrifuge tubes, water is added to centrifuge 4- through ultrafiltration
It 5 times, is dispersed in physiological saline, obtains 0.1mL nano-probes MNPs-DSPE-PEG-RGD-I125(504 μ Ci), radioactivity
It learns and pure is more than 95%.Take 0.1mL nano-probes MNPs-DSPE-PEG-RGD-I125Tail vein injection to U87MG kinds are planted
BALB/C nude mices, the SPECT imagings at observation 1h, 3h, 6h time point.
Embodiment 8
Take the nano-probe MNPs-DSPE-PEG-RGD aqueous solutions being prepared in 0.1mL embodiments 1 and NaI125
(6.37mCi, 150mg) adds in a concentration of 4mg/mL chloramine-Ts of 100 μ L as in sample cell, after shaking 5min, adds in 200 μ L
A concentration of 5mg/mL Sodium Metabisulfites terminate reaction, and reaction solution is transferred in 10K ultra-filtration centrifuge tubes, add water through ultrafiltration from
Heart 4-5 times is dispersed in physiological saline, obtains 0.5mL nano-probes MNPs-DSPE-PEG-RGD-I125(1.22mCi), radiation
Property chemistry pure be more than 95%.Take 0.2mL nano-probes MNPs-DSPE-PEG-RGD-I125(496 μ Ci) tail vein injection is extremely
U87MG kinds plant BALB/C nude mices, observation 1h, 3h, 6h, 12h, for 24 hours, the SPECT at 48h time points imaging.
Fig. 7 is the MNPs-DSPE-PEG-RGD-I in the present embodiment125Tail vein injection is naked in the BALB/C that U87MG kinds are planted
Mouse tumour SPECT imaging figures, it can be seen that after tail vein injection nano molecular image is visited, can be seen at tumour in 1-18h
Apparent to image, signal is most strong at 6h tumours, images at rear tumour slowly weaken for 24 hours.The liver region in entire videograph process
Imaging is in decrease slowly.As a result show that nano molecular image visits MNPs-DSPE-PEG-RGD-I125With preferable targeting,
Imaging for tumour provides support.
Embodiment 9
Before nano-probe is injected, MRI is imaged and writes down T at the BALB/C nude mouse tumors of U87MG cell seedings2It is weighted to
The signal value of picture.The nano-probe aqueous solution of MNPs-DSPE-PEG-RGD obtained in 1mL embodiments 1 is taken to be centrifuged through ultrafiltration, point
Dissipate in 0.2mL physiological saline, in the BALB/C nude mices of tail vein injection to U87MG cell seedings, observation 1h, 3h, 6h, 12h,
For 24 hours, T at 48h time point tumours2Weighted imaging writes down the signal value of weighted imaging at corresponding time point tumour.
Fig. 6 shows that nano molecular image probe MNPs-DSPE-PEG-RGD tail vein injections are in U87MG in the present embodiment
MRI imagings figure under 7.0T at the BALB/C nude mouse tumors of plantation, we can be found that at tumour opposite T after 1-6h is injected2
The signal value of weighted imaging is enhancing, and 6h images are compared with the image before injection after injection, and signal is apparent at tumour
It is dimmed, weighted imaging signal value Δ T2/T2Value before injection than increasing 50%.The result shows that nano-particle MNPs-DSPE-PEG-
RGD has shown well targeting T in vivo2Weighted imaging effect.
The above description of the embodiments is intended to facilitate ordinary skill in the art to understand and use the invention.
Person skilled in the art obviously can easily make these embodiments various modifications, and described herein general
Principle is applied in other embodiment without having to go through creative labor.Therefore, the present invention is not limited to above-described embodiment, abilities
Field technique personnel announcement according to the present invention, improvement and modification made without departing from the scope of the present invention all should be the present invention's
Within protection domain.
Claims (7)
1. one kind has MRI/SPECT bimodal image cancer target multifunctional nano probes, which is characterized in that including by Fe@
Fe3O4Nano-particle is coupled at Fe@Fe3O4The liposome DSPE-PEG-RGD on nano-particle surface layer and liposome DSPE-PEG groups
Into MNPs-DSPE-PEG-RGD nano-probes；
Label has I on the MNPs-DSPE-PEG-RGD nano-probes125, and form MNPs-DSPE-PEG-
RGD-I125Nano-probe.
2. one kind according to claim 1 has MRI/SPECT bimodal image cancer target multifunctional nano probes,
It is characterized in that, a diameter of 12~13nm of the MNPs-DSPE-PEG-RGD nano-probes.
3. one kind according to claim 1 has MRI/SPECT bimodal image cancer target multifunctional nano probes,
It is characterized in that, the MNPs-DSPE-PEG-RGD-I125The radio chemistry of nano-probe is pure to be more than 95%.
4. a kind of have MRI/SPECT bimodal image cancer target multifunctional nano probes as claimed in claim 1 or 2
Preparation method, which is characterized in that include the following steps：DSPE-PEG-RGD and DSPE-PEG are dissolved in organic solvent, added in
Fe@Fe3O4Nano-particle solution is uniformly mixed, and is removed organic solvent, is added water, diafiltration obtains MNPs-DSPE-PEG-
RGD nano-probes；
Then, MNPs-DSPE-PEG-RGD aqueous solutions are configured, are charged with band I125Salt and chloramine-T aqueous solution, concussion carry out
Reaction adds and lays particular stress on sulfite solution and terminate reaction, to get to MNPs-DSPE-PEG-RGD-I after ultrafiltration centrifugation125It receives
Rice probe.
It is 5. according to claim 4 a kind of with MRI/SPECT bimodal image cancer target multifunctional nano probes
Preparation method, which is characterized in that DSPE-PEG-RGD, DSPE-PEG and Fe@Fe3O4The ratio between additive amount of nano-particle for (4~
6)：(7~13)：0.5.
It is 6. according to claim 4 a kind of with MRI/SPECT bimodal image cancer target multifunctional nano probes
Preparation method, which is characterized in that the organic solvent be chloroform, the Fe@Fe3O4Nano-particle solution for concentration 0.5~
The Fe@Fe of 1.5mg/mL3O4The ratio between nano-particle solution chloroformic solution, the additive amount of organic solvent, DSPE-PEG-RGD and water is
2mL：(4~6) mg：(3~7) mL；
Uniformly mixed process conditions are：Incubator overnight at room temperature；
The technique for removing solvent is rotated for room temperature；
The process conditions of diafiltration are：After 3500Da bag filters dialysis 48h, 0.22 μm of filtering with microporous membrane is used.
It is 7. according to claim 4 a kind of with MRI/SPECT bimodal image cancer target multifunctional nano probes
Preparation method, which is characterized in that the band I125Salt is NaI125, the weighting sulphite is Sodium Metabisulfite；
A concentration of 0.5~1.5mg/mL of the MNPs-DSPE-PEG-RGD aqueous solutions, a concentration of the 3 of chloramine-T aqueous solution
~5mg/mL lays particular stress on a concentration of 4~6mg/mL of sulfite solution；
MNPs-DSPE-PEG-RGD aqueous solutions, band I125Salt, chloramine-T aqueous solution and lay particular stress on sulfite solution additive amount it
Than for 1mL：(30~150) mg：(50~150) μ L：(150~250) μ L；
The time of concussion reaction is 4~8min.
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| CN201510898032.2A CN105412950B (en) | 2015-12-08 | 2015-12-08 | With MRI/SPECT bimodal image cancer target multifunctional nano probes and preparation and application |
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| CN106512029A (en) * | 2016-11-22 | 2017-03-22 | 上海师范大学 | Nano-probe with apoptosis target function and preparation and application |
| CN106492236B (en) * | 2016-11-22 | 2019-07-12 | 上海师范大学 | A kind of multifunctional nano probe and its preparation method and application |
| CN106955362B (en) * | 2017-03-08 | 2020-08-07 | 上海师范大学 | Application of nano probe in preparation of tumor targeted photoacoustic imaging signal medicine |
| CN109364246B (en) * | 2018-10-11 | 2021-07-09 | 南京鼓楼医院 | Magnetic resonance/activation type fluorescence bimodal imaging targeted photothermal diagnosis and treatment nano probe and synthetic method and application thereof |
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