CN115607690A - Molecular probe and preparation method and application thereof - Google Patents

Molecular probe and preparation method and application thereof Download PDF

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CN115607690A
CN115607690A CN202110803387.4A CN202110803387A CN115607690A CN 115607690 A CN115607690 A CN 115607690A CN 202110803387 A CN202110803387 A CN 202110803387A CN 115607690 A CN115607690 A CN 115607690A
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张茜
侯征
王璐瑶
胡荣军
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Abstract

The invention relates to the technical field of disease detection reagents, in particular to a CD47 nano molecular probe and a preparation method and application thereof. The multi-mode nano antibody molecular probe comprises a radioactive element E, a CD47 nano antibody and a T with a- (M) M-structural formula, wherein G is respectively connected with L 1 ‑R 1 And L 2 ‑R 2 Are connected in sequence. The molecular probe provided by the invention can realize near-infrared fluorescence single imaging, nuclide single imaging and two-mode combined imaging, and can be used for tumor treatment by combining specific nuclide besides tumor diagnosis.

Description

Molecular probe and preparation method and application thereof
Technical Field
The invention belongs to the technical field of molecular probes, and particularly relates to a CD47 nano molecular probe and a preparation method and application thereof.
Background
Besides high resolution, high sensitivity and fast imaging technology, the realization of in vivo imaging of specific targets also needs specific molecular probes. Molecular probes are the key to the success of imaging, and their synthesis and detection are one of the most popular and leading-edge problems in molecular imaging studies. However, in all the current molecular imaging technologies, no perfect imaging technology can provide all the information about the detected object, and any imaging technology has its own advantages and disadvantages; none of the conventional molecular probes provides information about all the structures, functions and molecules of the tissue. In order to overcome these drawbacks, people have begun to research bi-modal or multi-modal molecular probes, and combine the advantages of two or more modal probes, so that the molecular probes can obtain some completely new information in the aspects of diagnosis, treatment, monitoring, etc. At present, various molecular probes with different modes are effectively combined to initially form various novel dual-mode probes including PET-optical, SPECT-optical, PET-MRI and the like. These "integrated" bimodal molecular imaging probes will certainly become an important tool for future in vivo imaging. Not only do multimodal molecular imaging require advanced imaging equipment, but also the development of new and efficient molecular probes. The existing molecular imaging technology has defects in the aspects of resolution, detection limit, availability, energy extensibility and the like, and the construction of a novel multi-modal molecular probe which is safe and effective and has detection and treatment functions is an important direction for future development.
CD47 is a widely expressed membrane protein, also known as integrin-associated protein (IAP). The interaction of the ligand of the Signal regulatory protein alpha (SIRP alpha) on the surfaces of macrophages and myeloid cells and the SIRP alpha provides a negative regulation Signal for phagocytes, and inhibits the phagocytosis of the macrophages. CD47 is a multifunctional receptor involved in interactions between tumors, tumor and stroma, and tumor and immune cells. In recent years, CD47 has been found to be overexpressed in a variety of human tumors. The over-expression of CD47 in human tumors and its use as an 'eat me' signal for tumors makes the CD47-SIRP alpha pathway an ideal target for various tumor immunotherapies. The more studied therapeutic approach is currently blocking antibodies that target CD47 directly. The nano antibody is a variable region fragment of a heavy chain antibody with a naturally deleted light chain in a camel, and is the smallest single-domain antibody with a complete antigen binding function at present. Compared with the traditional monoclonal antibody, the nano antibody has the advantages of small molecular volume, strong tissue penetration capacity, higher stability, easy binding with protein fissure epitopes, low production cost and the like, and becomes a promising candidate molecule for developing a new generation of therapeutic antibody.
Disclosure of Invention
In view of the above, it is an object of the present invention to provide a multi-modal molecular probe with a novel structure based on CD47 nanobody. The molecular probe has targeting effect on various tumors over expressing CD47, and can perform in vivo imaging in radionuclide and/or optical modes.
Another objective of the invention is to provide a preparation method of the CD 47-targeted multi-modal molecular probe.
The invention also aims to provide application of the multi-modal molecular probe targeting CD47 in preparing a colon cancer diagnosis and treatment medicine.
In order to achieve the above object, the present invention provides the following technical solutions:
a multi-modal nanobody molecular probe having the following structure:
Figure BDA0003164534270000021
d is a CD47 nanobody;
e is a radioactive element 125 I, 126 I, 130 I, 131 I or H;
t is selected from the following structures:
said L is 1 And L 2 Having the formula- (M) M-in which M represents a monomer which is identical to or different from one another and may be-CH 2 -、-CH 2 CH 2 O-、-C(＝O)-、-C(＝O)O-、-C(＝O)NH 2 -, -S-S-, -O-, -S-, -NH-C (SC) -C (= O) -or-HC = CH-, SC is the residue of 20 natural amino acids, M is the number of monomer repeats and is an integer between 0 and 60, and M can also be selected from the following structures:
Figure BDA0003164534270000022
R 1 is a metal ion complexing group or a fluorescent group and is selected from the following structures:
Figure BDA0003164534270000031
R 2 can be reacted with R 1 Are the same or different when R 2 And R 1 At different times, R 2 Is a metal ion complexing group, a fluorescent group, a steroid group or a PEG group.
For a targeted fluorescent probe, sufficient binding time of the probe molecule to the target is required to achieve sufficient TBR (tumor to background ratio, T/B). Studies have shown that the binding time is largely dependent on the dissociation rate of the probe-target complex, i.e., k off . The effectiveness of the probe depends on the dissociation process, probe-target binding rate constant k on Limited by concentration and diffusion rate and thus difficult to control. And k is off It is entirely dependent on the specific interaction between the probe and its target binding. Monovalent ligand-receptor interactions are primarily enthalpy-driven processes in which the ligand diffuses to the target in solution and binds to the receptor with a free energy of interaction ag = Δ H-T Δ S, where Δ G is the free energy binding force and is the sum of the enthalpy (Δ H) and entropy (-T Δ S) contributions. Only two states, bound and unbound, exist in a monovalent system. In a multivalent system, the scaffold itself and the attachment of multiple ligands to the scaffold, the entropy penalty required for binding of multivalent probes to the target can be reduced by judicious design of the linkers.
The invention aims to design a novel fluorescent molecular probe, wherein the improvement of TBR (tumor background ratio, T/B) is realized by improving TBR, increasing T or reducing B, the effective method for increasing T is to prolong the action time of the probe and a target, and the effective method for prolonging the action time of the probe and the target is to reduce k off . The linker in the monovalent probe of the present invention enhances targeted fluorescent molecular probesAffinity between the needle and the target, and multivalent probes can further enhance affinity. (polyvalent vs. monovalent, k) off This is greatly reduced, see Multivalency: concepts, research and Applications, edited by Jurraan Huskens, leonard J.Prins, rainer Haag, bart Jan Ravoo, pp 209).
As a preferred embodiment, the fluorescent molecular probe has a structure represented by formula I:
Figure BDA0003164534270000041
the invention also provides a preparation method of the fluorescent molecular probe, which comprises the following steps:
the CD47 nano antibody reacts with the reagent 1 to generate an intermediate product 2, the intermediate product 2 further reacts with the reagent 3 to obtain an intermediate product 4, and the intermediate product 4 reacts with the reagent 5 to generate a molecular probe 6:
Figure BDA0003164534270000042
wherein A is one of the following structural formulas:
Figure BDA0003164534270000043
wherein B is one of the following structural formulas:
Figure BDA0003164534270000051
in reagent 2, c has the following structural formula:
Figure BDA0003164534270000052
the E and L 1 、L 2 、R 1 、R 2 The same as the above-mentioned limits.
The invention also provides a nuclide imaging agent comprising a molecular probe as described above, wherein R is 1 And R 2 At least one of which is a metal ion complexing agent, with 65 Ga、 64 Cu or 89 Zr ions are combined.
The invention also provides a near-infrared fluorescent tracer, which comprises the molecular probe, wherein at least one of R1 and R2 is a near-infrared fluorescent group.
The invention also provides a multi-modal probe which has the structure as described above, wherein R 1 And R 2 Are respectively and 65 Ga、 64 cu or 89 Zr ion combined metal ion complex group and near infrared fluorescent group.
The invention also provides a multi-mode probe which has the structure as described above, R 1 And R 2 Is a near-infrared fluorescent group, and the fluorescent group is a fluorescent group, 125 i replaces hydrogen on tyrosine of the CD47 nano antibody.
The molecular probe provided by the invention is used for preparing a reagent for tumor diagnosis and treatment.
The nuclide imaging agent, the near-infrared fluorescent tracer and the multi-modal probe are used for preparing a reagent for tumor diagnosis and treatment.
The invention also provides a composition comprising a molecular probe as described in any of the above and a pharmaceutically acceptable carrier.
The carrier is conventionally selected by those skilled in the art as needed, and may be selected from, for example, sodium dihydrogen phosphate, disodium hydrogen phosphate, sodium chloride, citric acid, sodium citrate, polysorbate 20, polysorbate 80, water for injection, and the like.
Compared with the prior art, the invention has the following beneficial effects:
1) The molecular probe provided by the invention can realize near-infrared fluorescence single imaging, nuclide single imaging and two-mode combined imaging, and can be used for tumor treatment by combining specific nuclide besides tumor diagnosis;
2) The CD47 nano antibody is used, so that the target binding specificity is high; the nano antibody has more advantages in the aspects of volume, tissue permeability and the like, so that the probe provided by the invention has higher imaging speed.
Drawings
FIG. 1 is a near-infrared fluorescence imaging spectrum of a nano antibody probe HCT116 subcutaneous tumor model.
FIG. 2 is a SPECT/CT scanning map of a nano-antibody probe HCT116 subcutaneous tumor model imaging.
Detailed Description
The invention discloses a molecular probe with a novel structure and a preparation method and application thereof, and a person skilled in the art can appropriately improve process parameters by referring to the content. It is expressly intended that all such similar substitutes and modifications which would be obvious to one skilled in the art are deemed to be included in the invention. While the methods and applications of this invention have been described in terms of preferred embodiments, it will be apparent to those of ordinary skill in the art that variations and modifications in the methods and applications described herein, as well as other suitable variations and combinations, may be made to implement and use the techniques of this invention without departing from the spirit and scope of the invention. The following description is given with reference to examples. Wherein the equivalents are molar equivalents in the examples.
Example 1
Intermediate product 1 synthesized by coupling CD47 nano antibody and isomeric functional crosslinking reagent DBCO-NHS
Figure BDA0003164534270000061
Dissolving 25mgCD47 nano antibody in physiological saline at room temperature to prepare 1mLCD47 nano antibody solution, adding 1mL 1.0M PBS (phosphate buffer solution) with pH8.5, and mixing to prepare CD47 nano antibody solution; 4 equivalents of DBCO NHS were dissolved in 20. Mu.L of DMSO, added to the CD47 nanobody solution, and incubated in a warm water bath at 20 ℃ for 2h with shaking for several times. After the reaction was completed, the reaction mixture was centrifuged at 1200rpm for 4 times using a desalting column (Pierce Zebra,5 mL) and 0.01M PBS as a mobile phase; the filtrate was collected and lyophilized to give 15mg of Compound 3.
Example 2
Synthesis of intermediate compound 4:
Figure BDA0003164534270000071
25mg of compound 2 (0.165mmol) and 98mg of compound 3 (0.33mmol) were dissolved in 2mL of DMF, and 57mg of K (0.42mmol) was added 2 CO 3 Heating to 80 ℃ for reaction for 4 hours, adding 2ml of water for cooling, purifying by high performance liquid chromatography, and freeze-drying the solvent to obtain 45mg of fluffy compound, wherein the detection conditions are as follows: type of chromatographic column: agela C18 (10 μm,
Figure BDA0003164534270000072
50X 250mm, chromatographic conditions: mobile phase a was 0.05% trifluoroacetic acid, mobile phase B was 90% acetonitrile/water, acetonitrile: water =90%:10% at a flow rate of 25 ml/min and a UV detection wavelength of 254 nm, and freeze-dried to give 45mg of Compound 4 (yield: 41%, purity 95.5%).
Example 3
Synthesis of intermediate compound 5:
Figure BDA0003164534270000073
45mg,0.068mmol of Compound 4 was dissolved in 1mL of DCM, and a solution of trifluoroacetic acid in dichloromethane (TFA/CH) was added to the above solution 2 Cl 2 Volume ratio =1:3,0.4 mL), reacted at room temperature for 45min, volatile matter was removed under reduced pressure, 2mL of water was added and lyophilized to obtain 16mg of compound 5 yield: 50.9%, purity 95%).
Example 4
Synthesis of intermediate compound 7:
Figure BDA0003164534270000081
compound 5 (2mg, 0.004mmol) was dissolved in 0.5mL of PBS (pH = 8.4) buffer, 0.5mL of PBS (pH = 8.4) buffer in which IR Dye 800CW NHS (compound 6) (10 mg) was dissolved was added, reacted at room temperature for 60min, purified by high performance liquid chromatography, and freeze-dried to obtain 6mg of compound 7 (yield 57%. Purity 94.6%). Wherein, the operating conditions of the high performance liquid purification are as follows: mobile phase a was 0.05% trifluoroacetic acid and mobile phase B was 90% acetonitrile/water (acetonitrile: water =90%: 10%), flow rate 25 ml per minute, uv detection wavelength 254 nm.
Example 5
Synthesis of intermediate compound 8:
Figure BDA0003164534270000091
10mg of Compound 3 obtained in example 1 was dissolved in 1mL of an aqueous solution, 2mg of Compound 7 was dissolved in 100. Mu.L of DMSO, and the two solutions were mixed well, shaken for 30 seconds, and reacted at room temperature for 45 minutes. After the reaction was completed, the reaction mixture was centrifuged 3 times at 1200rpm using a desalting column (Pierce Zebra,5 mL) and 0.01M PBS as a mobile phase. The filtrate was collected and lyophilized to give 6mg of compound 8.
Example 6
Synthesizing a multi-modal probe:
Figure BDA0003164534270000101
100 μ L (2 mg/mL) of compound 8 was taken, 100 μ L of 0.02mol/L pH7.4 phosphate buffer solution and 15 μ L of Na125I (2.54 mCi) solution were added, mixed, 20 μ L of 5mg/mL chloramine T solution was added, the mixture was allowed to react at room temperature for 70 seconds on a mixer, 200 μ L of sodium metabisulfite solution (5 mg/mL) was added, followed by 2.06mL of 0.02mol/L pH7.4 phosphate buffer solution, the reaction was continued for 5 minutes, separation was performed with a PD10 column, the eluate was 0.02mol/L pH7.4 phosphate buffer solution, and the multi-modal probe was obtained by collecting and eluting through separate tubes.
Test examples
1. Establishing a tumor model
All animal experimental procedures were performed at the Suzhou university laboratory animal center and the Suzhou university Committee for animal protection and useWill proceed with approval. To establish a model of subcutaneous tumor of HCT-116-bearing colon carcinoma, healthy Balb/C nude mice (18-22 g) were used and injected with 50. Mu.L of HCT-116 cell suspension (5X 10) at the right inguinal site of the mice 6 One cell). When the tumor volume reaches about 200mm 3 And starting living body near infrared fluorescence imaging and microSPECT-CT scanning imaging.
2. Near-infrared fluorescence imaging
Nude mice of 9 HCT-116 subcutaneous tumor models were randomly divided into 3 groups of 3 mice each. The CD47 nano antibody multi-modal molecular probe obtained in example 6 is injected through tail vein, the dosage is 2.5mg/kg, 5mg/kg and 10mg/kg respectively, and the injection volume is 200 mu L. The IVIS spectrum small animal three-dimensional living body imager of Perkin elmer is opened, and the CCD lens is initialized to-90 ℃. And opening the gas anesthesia instrument for the small animals, adjusting the concentration of isoflurane to 5%, and adjusting the concentration of isoflurane to 3% after the mice are anesthetized until the scanning is finished. The anesthetized mice are placed in order in a scanning area, and the nose tip is placed in the vent hole. The excitation and emission wavelengths of the scan (theoretical Em =789, ex =774; actual Em =840, ex = 745) were set and scanned at 2, 4, 8, 24, 48 hours post-dose, and the results of the mouse imaging are shown in fig. 1.
MicroSPECT-CT scan imaging
The CD47 nanobody multimodal molecular probe obtained in example 6 was injected into 3 HCT-116 subcutaneous tumor model mice via tail vein, at a dose of 5mg/kg and an injection volume of 200. Mu.L. Mice were anesthetized with a mixture of isoflurane and oxygen at a ratio of 1.5% and a flow rate of 0.6L/min. Scanning is carried out at 2, 4, 8, 24 and 48 hours by using microSPECT-CT, and CT imaging parameters are bulb tube current (615 mu A), bulb tube voltage (55 kV), an accurate scanning mode and an all-round scanning mode, and the scanning time is 12 minutes. The SPECT scan time was 15min. The imaging effect is shown in fig. 2.
Near-infrared and microSPECT-CT results show that the enrichment starts at the tumor site 2 hours after injection in example 6, which shows that the probe has good targeting property for HCT-116 colon cancer tumor, can realize accurate positioning of the tumor, and the tumor enrichment can reach 48 hours, which shows that the imaging of the multi-modal molecular probe based on the CD47 nano antibody is fast and long in duration. Compared with the molecular probe based on the full-length monoclonal antibody, the molecular probe based on the full-length monoclonal antibody usually needs to be obviously imaged within about 72 hours after injection, and the probe based on the nano antibody has obvious advantages in imaging time, can be more suitable for clinical application scenes and has more clinical transformation advantages.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.

Claims (10)

1. A multi-modal nanobody molecular probe, characterized by the following structure:
Figure FDA0003164534260000011
d is a CD47 nano antibody;
e is a radioactive element 125 I, 126 I, 130 I, 131 I or H;
t is selected from the following structures: has the following structure:
Figure FDA0003164534260000012
said L 1 And L 2 Having the formula- (M) M-in which M represents a monomer which is identical to or different from one another and may be-CH 2 -、-CH 2 CH 2 O-、-C(＝O)-、-C(＝O)O-、-C(＝O)NH 2 -, -S-S-, -O-, -S-, -NH-C (SC) -C (= O) -or-HC = CH-, SC is the residue of 20 natural amino acids, M is the number of monomer repeats and is an integer between 0 and 60, and M can also be selected from the following structures:
Figure FDA0003164534260000013
R 1 is a metal ion complexing group or a fluorescent group and is selected from the following structures:
Figure FDA0003164534260000021
R 2 can be reacted with R 1 Are the same or different when R 2 And R 1 At different times, R 2 Is a metal ion complexing group, a fluorescent group, a steroid group or a PEG group.
2. The fluorescent molecular probe of claim 1, wherein the fluorescent molecular probe has a structure represented by formula i:
Figure FDA0003164534260000022
3. the method for preparing a fluorescent molecular probe according to any one of claims 1 to 2, comprising the steps of:
the CD47 nano antibody reacts with the reagent 1 to generate an intermediate product 2, the intermediate product 2 further reacts with the reagent 3 to obtain an intermediate product 4, and the intermediate product 4 reacts with the reagent 5 to generate a molecular probe 6:
Figure FDA0003164534260000031
wherein A is one of the following structural formulas:
Figure FDA0003164534260000032
wherein B is one of the following structural formulas:
Figure FDA0003164534260000033
in reagent 2, c has the following structural formula:
Figure FDA0003164534260000034
the E and L 1 、L 2 、R 1 、R 2 The scope of which is defined in claim 1.
4. A nuclide imaging agent comprising the molecular probe as defined in claim 1 wherein R 1 And R 2 At least one of which is a metal ion complexing agent, with 65 Ga、 64 Cu or 89 Zr ions are combined.
5. A near-infrared fluorescent tracer comprising the molecular probe of claim 1, wherein at least one of R1 and R2 is a near-infrared fluorophore.
6. A multimodal probe having the structure of claim 1, wherein R 1 And R 2 Are respectively and 65 Ga、 64 cu or 89 Zr ion combined metal ion complex group and near infrared fluorescent group.
7. A multimodal probe having the structure of claim 1, R 1 And R 2 Is a near-infrared fluorescent group, and the fluorescent group is a fluorescent group, 125 i replaces hydrogen on tyrosine of the CD47 nanobody.
8. Use of the fluorescent molecular probe according to any one of claims 1-2 in the preparation of a reagent for tumor diagnosis and treatment.
9. Use of the nuclide imaging agent as defined in claim 4, the near-infrared fluorescent tracer of claim 5, or the multimodality probe of claim 6 or 7 for the preparation of a reagent for tumor diagnosis and treatment.
10. A composition comprising the fluorescent molecular probe of any of claims 1-2 and a pharmaceutically acceptable carrier.
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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106281306A (en) * 2015-06-13 2017-01-04 复旦大学 The near-infrared fluorescent group of reversible instruction physiological phenomenon environment
CN108219782A (en) * 2018-04-11 2018-06-29 江苏省人民医院（南京医科大学第附属医院） Near-infrared fluorescent probe, multi-modal nano contrast agent based on probe, preparation and application thereof
CN108514647A (en) * 2018-05-30 2018-09-11 苏州艾渂鑫生物医药技术有限公司 Multi-modal molecular image probe of MMP-2 specificity and preparation method thereof and the application in preparing tumor imaging agent
CN110684017A (en) * 2019-09-20 2020-01-14 苏州大学 High-stability near-infrared two-region small-molecule fluorescent probe and preparation method and application thereof
CN110885376A (en) * 2018-09-11 2020-03-17 上海洛启生物医药技术有限公司 anti-CD 47/CD20 bispecific antibodies and uses thereof
CN110981959A (en) * 2019-11-19 2020-04-10 深圳普瑞金生物药业有限公司 CD47 single domain antibody, nucleotide sequence, expression vector and kit

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106281306A (en) * 2015-06-13 2017-01-04 复旦大学 The near-infrared fluorescent group of reversible instruction physiological phenomenon environment
CN108219782A (en) * 2018-04-11 2018-06-29 江苏省人民医院（南京医科大学第附属医院） Near-infrared fluorescent probe, multi-modal nano contrast agent based on probe, preparation and application thereof
CN108514647A (en) * 2018-05-30 2018-09-11 苏州艾渂鑫生物医药技术有限公司 Multi-modal molecular image probe of MMP-2 specificity and preparation method thereof and the application in preparing tumor imaging agent
CN110885376A (en) * 2018-09-11 2020-03-17 上海洛启生物医药技术有限公司 anti-CD 47/CD20 bispecific antibodies and uses thereof
CN110684017A (en) * 2019-09-20 2020-01-14 苏州大学 High-stability near-infrared two-region small-molecule fluorescent probe and preparation method and application thereof
CN110981959A (en) * 2019-11-19 2020-04-10 深圳普瑞金生物药业有限公司 CD47 single domain antibody, nucleotide sequence, expression vector and kit

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YASSER E. A. SHAHEIN等: "Molecular cloning and functional characterization of the pig homologue of integrin-associated protein (IAP/CD47)", 《IMMUNOLOGY》, vol. 106, pages 564 - 576 *

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