CN107198779A - A kind of nanometer coupled complex of stem cell labeling spike and targeting navigation and its preparation method and application - Google Patents
A kind of nanometer coupled complex of stem cell labeling spike and targeting navigation and its preparation method and application Download PDFInfo
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- CN107198779A CN107198779A CN201710298602.3A CN201710298602A CN107198779A CN 107198779 A CN107198779 A CN 107198779A CN 201710298602 A CN201710298602 A CN 201710298602A CN 107198779 A CN107198779 A CN 107198779A
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Abstract
The invention discloses nanometer coupled complex of a kind of stem cell labeling spike and targeting navigation and its preparation method and application; the compound is made up of three functional modules; the carriers such as nano particle or macromolecule that nucleus module is made up of one or more of reagents with imaging function; mark module is coupled on nucleus module and with the part of specific binding stem cell surface molecular function, and targeting module is to be coupled on nucleus module and the part with specific recognition pathological tissues function.Compound is combined and stem cell surface by its mark module, and targetting module by it plays targets identification effect, guides stem cell target pathological tissues, and can carry out imaging in vivo and spike to stem cell with reference to one or more of medical imaging devices.
Description
Technical field
The present invention relates to a kind of nano target and mark tracer technique, belong to nano biological medical domain, more particularly to one
Plant nanometer coupled complex of stem cell labeling spike and targeting navigation and its preparation method and application.
Technical background
Stem cell (stem cell) is the multipotential cell that a class has the of self-replication capacity.Under certain condition, it can
To be divided into a variety of functioning cells.Cellular replacement therapy is in healthy stem cell transplantation to patient's body, to reach reparation
Or replace damaged cell or tissue, the regeneration function of body own cells stimulated, so as to reach the purpose of healing.Stem cell transplantation
Therapeutic domain is very wide, can typically treat the nervous system disease, disease of immune system, also have some other Medicine and Surgery diseases.By
In stem cell in the significance in disease treatment field, widely studied and applied.
In order to during studying cellular replacement therapy, flyway, Tissue distribution and target device of the stem cell in body
Official, time-to-live, the interaction with pathological tissues and therapeutic effect etc., people have developed the skill of some labeled stem cells
Art, such as fluorescence labeling (organic fluorescent dye, fluorescin, fluorescence quantum), magnetic nanoparticle mark etc., these marks
Cell membrane or internalization are generally marked to intracellular, spike is carried out by using Imaging-PAM and mr imaging technique.
Fluorescent labelling techniques are although simple and convenient, sensitivity is high, but in living animal or during applied to clinic, because light is to tissue
Penetration depth is inadequate, spatial discrimination is low, causes using limited.Magnetic marker technology combination magnetic resonance imaging is a preferably solution
Scheme, magnetic nanoparticle has higher image contrast, and has been applied to the magnetic resonance contrast agent and tumour of clinic
Thermotherapy magnetic nanoparticle, safety issue is guaranteed, and magnetic resonance imaging can provide anatomy imaging and high space again
Resolution ratio, suitable for live body dynamic tracer and evaluation.But, basic research and clinical application research with stem-cell therapy disease
Development, stem-cell therapy technology, which is proposed, to be needed in higher requirement, mechanism after further clear and definite stem cell enters in vivo
Distribution, differentiation and the interaction of target organ and home to return to, technically need derived techniques cooperative compensating, can realize many
Mould imaging instruct accurate stem-cell therapy, while by labelling technique can also assign stem cell target, differentiation etc. additionally
Function.Develop a kind of new multi-modal, versatile stem cell labelling technique therefore, needing badly, further promote stem cell basis to grind
The development with clinical application research is studied carefully, to realize that stem cell precisely treats the strong instrument of offer.
The content of the invention
Examined the invention aims to the basic problem and medical science for solving stem cell labeling, targeting and medical imaging spike
Treatment demand, it is proposed that the nanometer technology comprehensive solution that can be solved the above problems simultaneously.
For achieving the above object, the present invention is adopted the following technical scheme that：
A kind of stem cell labeling spike and the nanometer coupled complex of targeting navigation, the compound is by three functional module groups
Into nano particle or macromolecule carrier that nucleus module is made up of one or more of reagents with imaging function mark mould
Block is coupled on nucleus module and with the part of specific binding stem cell surface molecular function, and it is to be coupled to target module
On nucleus module and with specific recognition pathological tissues function part.
It is described constitute nucleus module imaging function reagent by one or more of contrast medium by with nano particle or height
Being combined for molecular vehicle, constitutes the nucleus module with single modality or multi-modality imaging function, its size is in 10-
Between 1000nm.The contrast medium be magnetic resonance imaging contrast agent (such as Gd coordination compound, ferroferric oxide nano granules) or
CT imaging contrasts (such as contain iodine compound, gold nano grain) or radio nuclide imaging contrast medium is (such as125I、18F etc.) or ultrasound
Imaging contrast (such as microbubble, nano bubble) or optical imaging contrast's agent (such as indocyanine green, fluorescence quantum).
The part for constituting mark module includes antibody (such as anti-CD105 antibody, anti-CD90 antibody), antigen and (is such as directed to
Be marked at the antibody on stem cell) or aptamers (such as stem cell surface CD146, CD271 nucleic acid be adapted to
Body) or biotin (for the labeled Avidin of stem cell surface) or Avidin (marked for stem cell surface
The biotin of note), zymolyte (as having the small molecule of specific affinity for some enzymes of stem cell surface) or polypeptide be (as used
The specific polypeptide that phage display peptide library comes out, has specific binding for stem cell surface CD105, CD90 etc.) or change
Learning medicine (such as some stem cell target small-molecule drugs) has the biology of specific binding stem cell surface molecular function
Macromolecular, polymer or small molecule；The composition mark module is combined in nucleus module by active forces such as chemical bond, absorption
Surface.
The part for constituting targeting module includes antibody (such as the anti-sclerostin antibodies for osteoporosis or for class
The adalimumab of rheumatic arthritis or the antibody for being such as directed to matrix metalloproteinase height expression after heart infarction is fallen ill) or
Person's antigen (such as the antibody for being marked at diseased region) or aptamers are (as being directed to some protein markers of diseased region
Aptamer) or biotin (as being marked at the Avidin of diseased region) or Avidin (as
The labeled biotin in diseased region) or zymolyte (as there is the small molecule of specific affinity for some enzymes of diseased region)
Or polypeptide is (such as the Duramycin polypeptides or Annexin V for myocardial damage apoptosis feature or for heart infarction and brain soldier
The RGD cyclic peptide of new vessels after middle generation) or chemicals (as heart infarction fall ill after matrix metalloproteinase height expression
Inhibitor) etc. have specific recognition pathological tissues functional biological macromolecular, polymer or small molecule；It is described to constitute targeting mould
The part of block is combined on nucleus module surface by active forces such as chemical bond, absorption.
The stem cell labeling spike and the nanometer coupled complex of targeting navigation, nucleus module are located in compound
The heart, mark module is incorporated into the surface of nucleus module with targeting module, and the two can be evenly distributed on nucleus module surface, also may be used
With mal-distribution on nucleus module surface.
The nanometer coupled complex is incorporated into stem cell surface by mark module, does not occur internalization, it is ensured that multiple
Compound is marked at stem cell surface, and outer end targeting module can play the function of targets identification pathological tissues.
The nanometer coupled complex of the stem cell labeling spike and targeting navigation can be applied to stem cell labeling, while energy
Stem cell target pathological tissues are guided, and one or more of medical imaging devices can be combined imaging in vivo is carried out to stem cell and is shown
Track.
It is as follows that the nanometer coupled complex of stem cell labeling spike and targeting navigation is typically prepared method：
(1) nano-carrier for including one or more of image tracers is built as core mould using nanometer composite technology
Block, such as compound of magnetic ferroferric oxide nanometer particle and fluorescence molecule can realize magnetic resonance/fluorescent dual module state imaging, Jenner
The compound of rice grain and fluorescence molecule can realize CT/ fluorescent dual modules state imaging, carried magnetic nano particle nano bubble can
Realize magnetic resonance/ultrasonic double-mode state imaging；
(2) modification of nucleus module surface biocompatible molecule, according to the chemical feature on nano-complex surface, selection
Macromolecule or biomolecule with functional group, are combined on nucleus module surface, modification by active forces such as chemical bond, absorption
Molecule outer end should remain with functional group, for further be coupled mark module with targeting module；
(3) there is the molecule of specific binding capacity to be mark module to stem cell for selection, and selection has to diseased region
The molecule of selectively targeted ability is respectively or same by mark module and targeting module using chemical coupling techniques as targeting module
When be coupled at nucleus module surface.
Beneficial effects of the present invention：There is nanometer coupled complex of the present invention stem cell labeling, targeting to lead simultaneously
Boat and the function of multi-modality imaging spike, to realize that the accurate stem-cell therapy that medical image is instructed provides powerful.
Brief description of the drawings
Fig. 1 is the nanometer coupled complex schematic diagram of stem cell labeling spike of the present invention and targeting navigation, wherein 1
It is mark module for nucleus module, 2,3 be targeting module.
Fig. 2 is the schematic diagram of magnetic/fluorescent dual module state nanometer coupled complex labeled stem cells described in embodiment 1, its
In 1 be cell, 2 be nucleus, and 3 be compound, 4 for the compound of cell surface marker partial enlargement, 5 be cell membrane surface
Antigen, 6 be magnetic nanoparticle, and 7 be fluorescence molecule, and 8 be the macromolecule layer of magnetic nanoparticle surface modification, and 9 be as mark
Remember the antibody of module, 10 be the aptamers as targeting module.
Embodiment：
Below in conjunction with the accompanying drawings and specific embodiment, the present invention is furture elucidated, it should be understood that these embodiments are only used for
The bright present invention rather than limitation the scope of the present invention, after reading this disclosure, those skilled in the art is to the present invention's
The modification of the various equivalent form of values falls within claims hereof limited range.
Compound of the present invention is made up of (as shown in Figure 1) three functional modules, and nucleus module is by with imaging work(
The carriers such as the nano particle or macromolecule of one or more of reagents composition of energy, mark module is to be coupled on nucleus module and have
There is the part of specific binding stem cell surface molecular function, targeting module is coupled on nucleus module and with specificity knowledge
The part of other pathological tissues function.Compound is combined and stem cell surface by its mark module, and targetting module by it plays
Targets identification is acted on, and guides stem cell target pathological tissues, and can combine one or more of medical imaging devices to enter stem cell
Row imaging in vivo and spike.Specific embodiment is as follows：
1 magnetic of embodiment/fluorescent dual module state stem cell labeling spike and the nanometer coupled complex of targeting navigation
The core component of the compound is by magnetic nanoparticle (such as ferroferric oxide nano granules) and fluorescence molecule (such as Yin
Diindyl cyanines are green) composition, magnetic nanoparticle surface uses macromolecule (such as the carboxyl polyethylene glycol, carboxylated Portugal of biocompatibility
Glycan, chitosan etc.) modified, fluorescence molecule by chemical bonds on the high molecular functional group of surface, remaining work(
Can group can be used to the mark modules such as chemical coupling antibody, polypeptide, aptamers and targeting module, mark module and targeting module with
Machine is distributed in nano grain surface.Specific preparation method is as follows：
(1) high temperature pyrolytic cracking (HTP) prepares oil-soluble Fe3O4@OA magnetic nanoparticles
0.7g ferric acetyl acetonade (Fe (acac) 3) is weighed in 100mL three-necked bottles, 20mL benzyl ether is added, adds
2mL oleic acid and 6mL oleyl amines.Under inert nitrogen gas (N2) protection, condensing reflux.The journey set according to programmable temperature controller
Sequence, reaction system is risen to after 220 DEG C, constant temperature 60min with 3.3 DEG C/min speed from room temperature, is continued with 3.3 DEG C/min speed
Rise to after 290 DEG C, constant temperature 30min, terminate reaction.Reaction product is cooled down at room temperature, and precipitation is washed with EtOH Sonicate Magneto separate,
In triplicate, the magnetic nanoparticle (Fe of oleic acid modified is obtained3O4@OA), size 10nm or so is scattered in standby in isooctane.
(2) ligand exchange prepares water solubility Fe3O4@PEG magnetic nanoparticles
Weigh 60mg double carboxyl terminal polyethylene glycol (COOH-PEG-COOH), 30mg natrium carbonicum calcinatums (Na2CO3), 6mg sulphurs
Acidifying-n-hydroxysuccinimide (solfo-NHS), 9mg dicyclohexylcarbodiimides (DCC), 3.9mg dopamine hydrochlorides
(DPA) it is placed in 100mL three-necked bottles, adds 6mL chloroforms and 3mL dimethylformamides (DMF), this hybrid reaction system is in room temperature
After lower standing 2h, with 450rpm speed stirring reaction 3h in 35 DEG C of water-baths, to prepare DPA-PEG-COOH.
Take oil-soluble magnetic nanoparticle (Fe3O4@OA) 15mg is slowly dropped into DPA-PEG-COOH hybrid reaction system
In, mixing speed is 200rpm, and reaction is stayed overnight.Next day stops reaction, and reactant is poured into beaker, n-hexane washing, carries out
Magneto separate, is precipitated as black particle shape material (Fe3O4@PEG magnetic nanoparticles), abandon supernatant, precipitation ultrasonic disperse to ultra-pure water
It is middle to form stable colloidal solution.PH value of solution is adjusted to 7, nano particle is not assembled.Sample through molecular cut off be 8~
14kDa bag filter dialysis 72h, with the membrane filtration that aperture is 0.22 μm, 4 DEG C save backup.
(3) magnetic of coupled antibody/fluorescence composite nanometer particle Fe3O4@PEG-ICG@Ab preparation
Take 1mg Fe3O4The@PEG magnetic nanoparticle aqueous solution, rubs according to-COOH: EDC: sulfo-NHS=1: 5: 15
Your ratio adds EDC (1- (3- dimethylamino-propyls) -3- ethyl carbodiimides, the 10mg/mL) aqueous solution and sulfo-NHS
The aqueous solution of (10mg/mL).Shaking table 100rpm shakes 30min.Ultrafiltration centrifugation (molecular weight 10KDa) remove free EDC and
Sulfo-NHS, by Fe3O4@PEG activating solution is concentrated into 900 μ L, adds 100 μ L pH8.0 borate buffer solution (0.2mol/
L).Proportionally add ICG (indocyanine green), mark module antibody and the target with amino terminal with amino-functional group
To module aptamers, shaking table is placed in, 100rpm concussions are stayed overnight.After reaction terminates, reaction solution is crossed post by S-300 gels and purified,
It is final purified probes sample to take initial cut filter liquor, is stored in the 1%BSA aqueous solution, protects antibody protein, it is to avoid lost
It is living.
Obtained compound has magnetic resonance imaging ability because of magnetic nanoparticle, because of fluorescence molecule with glimmering
Photoimaging ability, the two cooperative compensating is imaged and tracking function there is provided bimodal；Compound is incubated altogether in vitro with stem cell
Educate, compound is combined by mark module with stem cell surface, realize the magnetic marker and fluorescence labeling (Fig. 2) to stem cell；Will
In the stem cell injection animal body marked, the compound for being marked at cell surface is realized by the exposed targeting module in outside
Identification and combination to pathological tissues, so as to increase accumulation of the stem cell in target tissue.In addition, magnetic nanoparticle is also provided
Pass through the function of magnetic field navigation stem cell.For the living animal after injection of labelled stem cell, can using magnetic resonance imaging and
Imaging-PAM carries out joint dynamic tracer.
The CT/ fluorescent dual modules state stem cell labeling spike of embodiment 2 and the nanometer coupled complex of targeting navigation
The core component of the compound is made up of gold nano grain and fluorescence molecule (such as indocyanine green), gold nano grain table
Face is modified using the macromolecule (such as carboxyl and the polyethylene glycol of sulfydryl end, chitosan, albumin) of biocompatibility,
Fluorescence molecule is by chemical bonds on the high molecular functional group of surface, and remaining functional group can be used to chemical coupling and resist
The mark modules such as body, polypeptide, aptamers and targeting module, mark module and targeting module are randomly dispersed in nano grain surface.
Specific preparation method is as follows：
(1) prepared by gold nano grain：
The chlorauric acid solutions of 100ml 0.01% are heated to boiling, it is rapid in the rotating speed stirring with 650~700r/min
1.5ml1% citric acid three sodium solution is added, heating is kept stirring for.Gold chloride, which is added, quickly becomes ash after trisodium citrate
Color, subsequently becomes black, gradually becomes colour stable after red, about 10~15min and, to claret, stops heating, be placed on air
In be cooled to after room temperature constant volume to 100ml, 4 DEG C of refrigerators are preserved.
(2) nanogold surface antibody is coupled
By nanogold centrifugal purification, the 1/5 of original volume is concentrated into, the μ g of every milliliter of Au content=239.15.1ml concentrations are taken to receive
Meter Jin, uses 0.1M K2CO3PH value of solution is adjusted to about 9.5,78 μ g mark modules antibody and targeting are separately added into rapidly in concussion
Module antibody, mixing is shaken up, and stands 5min, and the BSA (bovine serum albumin(BSA)) for adding final concentration of 1% is closed, 4 DEG C of refrigerators
Preserve.Probe is under the conditions of 4 DEG C, and 12000rpm centrifugation 40min abandon supernatant, resuspension is deposited in the pH=9.0 aqueous solution.
(3) fluorescence molecule is coupled on nanogold surface protein
In nanogold obtained above-antibody coupling matter aqueous solution (pH=9.0), ICG is directly added under vortex conditions
NHS Acibenzolars, be placed in shaking table, 100rpm concussions 30min.Product is under the conditions of 4 DEG C, and 12000rpm centrifugation 40min are abandoned
Clearly, precipitation is resuspended in the 1% BSA aqueous solution, is preserved under the conditions of 4 DEG C.
Obtained compound because the gold nano grain of high atomic number and with CT imaging capabilities because fluorescence molecule and
With fluorescence imaging ability, the two cooperative compensating is imaged and tracking function there is provided bimodal；By compound and stem cell in vitro
It is incubated altogether, compound is combined by mark module with stem cell surface, realizes the gold mark and fluorescence labeling to stem cell；Will mark
In the stem cell injection animal body remembered, the compound for being marked at cell surface passes through the exposed targeting module realization pair in outside
The identification and combination of pathological tissues, so as to increase accumulation of the stem cell in target tissue.For the work after injection of labelled stem cell
Body animal, can carry out joint dynamic tracer using CT imagings and Imaging-PAM.
3 magnetic of embodiment/ultrasonic double-mode state stem cell labeling spike and the nanometer coupled complex of targeting navigation
The core component of the compound by carried magnetic nano particle (such as ferroferric oxide nano granules) ultrasonic nano
Bubble is constituted, and ultrasonic nano bubble is prepared from by PLA or PLGA as cyst wall, and inside includes sky
Carried magnetic nano particle on gas, cyst wall, nano bubble surface uses macromolecule (such as carboxylated polyethylene alcohol of biocompatibility
Deng) modified, surface carboxyl group can be used to the mark modules such as chemical coupling antibody, polypeptide, aptamers and targeting module, mark
Note module and targeting module are randomly dispersed in nano bubble surface.Specific preparation method is as follows：
(1) preparation of magnetic/ultrasonic nano bubble
0.5g PLAs (PLA) are dissolved in 10mL chloroforms, the Fe of 10nm or so Coated with Oleic Acid is pipetted3O4Nano particle
(preparing be the same as Example 1) chloroformic solution (5mg/mL, 5mL) is uniformly mixed with above-mentioned polymer solution, then again by 1mL distilled waters
In micro sorbester p17 injection solution, with sound and vibration instrument (power 200Ws-1) at the uniform velocity it is being passed through N2Surpass under conditions of (4mL/min)
Acoustic cavitation 10min, prepares W/O emulsion microbubbles；W/O emulsions are poured into 50mL 5.0% (mass fraction) carboxyl modified
In polyvinyl alcohol (PVA) aqueous solution, mechanical agitation (rotating speed 12000r/min) handles 2h, the obtained micro- gas of double emulsion at room temperature
Bubble, sample dispersion is collected in 10mL water through centrifuging after (4 DEG C, 15min, 10000r/min) separation.
(2) surface antibody is coupled
The ultrasonic microbubble water solution of magnetic of the above-mentioned preparations of 1mL is taken, according to-COOH: EDC: sulfo-NHS=1: 5: 15
Mol ratio adds EDC (1- (3- dimethylamino-propyls) -3- ethyl carbodiimides, the 10mg/mL) aqueous solution and sulfo-NHS
The aqueous solution of (10mg/mL), 100rpm shaking tables concussion 30min, carries out activated carboxylic.4 DEG C be centrifuged off free EDC and
Sulfo-NHS, 600 μ L are settled to water by precipitated product, add 400 μ L pH8.0 borate buffer solution (0.2mol/L,
Through containing mark module antibody and each 1mg of targeting module antibody), shaking table is placed in, 100rpm concussions are stayed overnight.After reaction terminates, from
The heart is washed 3 times, is stored in the 1%BSA aqueous solution, 4 DEG C of preservations.
Obtained compound has magnetic resonance imaging ability because of magnetic nanoparticle, has because of nano bubble structure
There is ultrasonic imaging capability, the two cooperative compensating is imaged and tracking function there is provided bimodal；Compound and stem cell is common in vitro
It is incubated, compound is combined by mark module with stem cell surface, realizes and the magnetic marker and nano bubble of stem cell are marked；Will
In the stem cell injection animal body marked, the compound for being marked at cell surface is realized by the exposed targeting module in outside
Identification and combination to pathological tissues, so as to increase accumulation of the stem cell in target tissue.After injection of labelled stem cell
Living animal, can carry out joint dynamic tracer using magnetic resonance imaging and ultrasonic imaging technique.
Claims (10)
1. a kind of stem cell labeling spike and the nanometer coupled complex of targeting navigation, it is characterised in that the compound is by three
Individual functional module composition, nano particle or macromolecule that nucleus module is made up of one or more of reagents with imaging function
Carrier, mark module is coupled on nucleus module and with the part of specific binding stem cell surface molecular function, targeting
Module is to be coupled on nucleus module and the part with specific recognition pathological tissues function.
2. a kind of stem cell labeling spike according to claim 1 and the nanometer coupled complex of targeting navigation, its feature
Be, it is described constitute nucleus module imaging function reagent by one or more of contrast medium by with nano particle or macromolecule
Being combined for carrier, constitutes the nucleus module with single modality or multi-modality imaging function, its size is in 10-1000nm
Between；The contrast medium be magnetic resonance imaging contrast agent or CT imaging contrasts or radio nuclide imaging contrast medium or ultrasound into
As contrast medium or optical imaging contrast's agent.
3. the nanometer coupled complex navigated according to a kind of stem cell labeling spike according to claim 2 and targeting, its
It is characterised by, the magnetic resonance imaging contrast agent is Gd coordination compound or ferroferric oxide nano granules；The CT imaging contrasts
Agent is containing iodine compound or gold nano grain；The radio nuclide imaging contrast medium is125I or18F；The ultrasonic imaging contrast medium
For microbubble or nano bubble；Optical imaging contrast's agent is indocyanine green or fluorescence quantum.
4. a kind of stem cell labeling spike according to claim 1 and the nanometer coupled complex of targeting navigation, its feature
Be, the part for constituting mark module include antibody or antigen or aptamers or biotin or Avidin or
Zymolyte or polypeptide or chemicals, the above-mentioned large biological molecule with specific binding stem cell surface molecular function,
Polymer or small molecule；The composition mark module is combined on nucleus module surface by active forces such as chemical bond, absorption.
5. a kind of stem cell labeling spike according to claim 4 and the nanometer coupled complex of targeting navigation, its feature
It is, antibody is anti-CD105 antibody or anti-CD90 antibody；The antigen is the antibody for being marked on stem cell；
The aptamers are the aptamer for stem cell surface CD146, CD271；The biotin is for stem cell surface
Labeled Avidin；The Avidin is for the labeled biotin of stem cell surface；The zymolyte be for
The some enzymes of stem cell surface have the small molecule of specific affinity；The polypeptide is the specificity come out using phage display peptide library
Polypeptide has specific binding for stem cell surface CD105, CD90；The chemicals is stem cell target small molecule
Medicine.
6. a kind of stem cell labeling spike according to claim 1 and the nanometer coupled complex of targeting navigation, its feature
Be, the part for constituting targeting module include antibody or antigen or aptamers or biotin or Avidin or
Zymolyte or polypeptide or chemicals, it is above-mentioned have specific recognition pathological tissues functional biological macromolecular, polymer or
Person's small molecule；The part for constituting targeting module is combined on nucleus module surface by active forces such as chemical bond, absorption.
7. a kind of stem cell labeling spike according to claim 6 and the nanometer coupled complex of targeting navigation, its feature
Be, the antibody be the anti-sclerostin antibodies for osteoporosis or the adalimumab for rheumatoid arthritis or
The antibody of matrix metalloproteinase height expression after person is directed to as fallen ill for heart infarction；The antigen is for being marked at lesion
The antibody at position；The aptamers are the aptamer for some protein markers of diseased region；The biotin is pin
Avidin to being marked at diseased region；The Avidin is the biotin for being marked at diseased region；It is described
Zymolyte is the small molecule for having specific affinity for some enzymes of diseased region；The polypeptide is for myocardial damage apoptosis feature
Duramycin polypeptides or Annexin V or after occurring for heart infarction and cerebral apoplexy new vessels RGD cyclic peptide；It is described
Chemicals is the inhibitor of matrix metalloproteinase height expression after being fallen ill for heart infarction.
8. a kind of stem cell labeling spike according to claim 1 and the nanometer coupled complex of targeting navigation, its feature
It is, nucleus module is located at the center of compound, mark module is incorporated into the surface of nucleus module with targeting module, the two can be with
Be evenly distributed on nucleus module surface, can also mal-distribution on nucleus module surface.
9. a kind of stem cell labeling spike according to claim 1 and the nanometer coupled complex of targeting navigation, its feature
It is, the compound is combined and stem cell surface by mark module, does not occur internalization, it is ensured that compound is marked at dry
Cell surface, outer end targeting module can play the function of targets identification pathological tissues.
10. the nanometer coupled complex of a kind of stem cell labeling spike and targeting navigation described in claim 1 can be applied to do
Cell marking, while stem cell target pathological tissues can be guided, and can combine one or more of medical imaging devices to stem cell
Carry out imaging in vivo and spike.
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