CN114984254B - Photoacoustic imaging contrast agent and application thereof - Google Patents
Photoacoustic imaging contrast agent and application thereof Download PDFInfo
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- CN114984254B CN114984254B CN202210641281.3A CN202210641281A CN114984254B CN 114984254 B CN114984254 B CN 114984254B CN 202210641281 A CN202210641281 A CN 202210641281A CN 114984254 B CN114984254 B CN 114984254B
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- 238000003384 imaging method Methods 0.000 title claims abstract description 27
- 239000002872 contrast media Substances 0.000 title claims abstract description 19
- 208000035143 Bacterial infection Diseases 0.000 claims abstract description 15
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract description 15
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 229910052797 bismuth Inorganic materials 0.000 claims description 11
- 239000000523 sample Substances 0.000 claims description 9
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 7
- 239000000463 material Substances 0.000 claims description 5
- 239000012621 metal-organic framework Substances 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 238000001514 detection method Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000006143 cell culture medium Substances 0.000 claims description 2
- 239000002953 phosphate buffered saline Substances 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 abstract description 11
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 238000004321 preservation Methods 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 230000001988 toxicity Effects 0.000 abstract description 2
- 231100000419 toxicity Toxicity 0.000 abstract description 2
- 229910001451 bismuth ion Inorganic materials 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 6
- 238000003745 diagnosis Methods 0.000 description 4
- 241000191967 Staphylococcus aureus Species 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 108010074051 C-Reactive Protein Proteins 0.000 description 2
- 102100032752 C-reactive protein Human genes 0.000 description 2
- 108010048233 Procalcitonin Proteins 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- ZREIPSZUJIFJNP-UHFFFAOYSA-K bismuth subsalicylate Chemical compound C1=CC=C2O[Bi](O)OC(=O)C2=C1 ZREIPSZUJIFJNP-UHFFFAOYSA-K 0.000 description 2
- 229960000782 bismuth subsalicylate Drugs 0.000 description 2
- KZFDVWZZYOPBQZ-UHFFFAOYSA-K bismuth;potassium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [K+].[Bi+3].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KZFDVWZZYOPBQZ-UHFFFAOYSA-K 0.000 description 2
- 238000013399 early diagnosis Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 229940046892 lead acetate Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
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- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 238000010895 photoacoustic effect Methods 0.000 description 2
- CWCXERYKLSEGEZ-KDKHKZEGSA-N procalcitonin Chemical compound C([C@@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)NCC(O)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H]1NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC1)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 CWCXERYKLSEGEZ-KDKHKZEGSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 108010042854 bacteria histone-like protein HU Proteins 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000090 biomarker Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 238000003501 co-culture Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000012631 diagnostic technique Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Acoustics & Sound (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Physics & Mathematics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ultra Sonic Daignosis Equipment (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention discloses a photoacoustic imaging contrast agent and application thereof, wherein the photoacoustic imaging contrast agent comprises Bi 3+ A donor and a solvent. Bi (Bi) 3+ Bismuth ions supplied by the donor can be combined with H produced by living bacteria 2 S reaction, generating photo acoustic signalA compound. The photoacoustic imaging contrast agent provided by the invention has high sensitivity and can detect early bacterial infection; can detect various bacterial infections and has wide adaptability; the components are simple and stable, the toxicity is low, and the low-temperature preservation is not needed.
Description
Technical Field
The invention relates to the field of medical detection, in particular to a photoacoustic imaging contrast agent and application thereof.
Background
Bacterial infections are local or systemic infections caused by invasion of pathogenic or conditionally pathogenic bacteria into the human body for growth and reproduction, production of toxins and other metabolites. Early bacterial infections have no obvious symptoms, which makes diagnosis of early bacterial infections difficult in clinical practice. Clinical practice often relies on changes in biomarkers of C-reactive protein (CRP), procalcitonin (PCT) and white blood cell count, which often lag behind the progression of infection, lacking specificity and infection location profile information. Photoacoustic imaging (PA) is a non-invasive biomedical diagnostic technique based on the photoacoustic effect. PA has advantages in terms of high optical contrast and deep tissue penetration, and PA can provide high contrast images and accurate real-time spatial evidence for diagnostic decision-making. In recent years, PA has great potential and rapid development in clinical applications such as dermatological imaging, vascular imaging, and musculoskeletal imaging. However, PA probes for infection diagnosis are still lacking. Therefore, there is an urgent need to develop a new class of PA probes that can be specifically turned on in response to the infectious microenvironment and achieve accurate early diagnosis of infection.
Disclosure of Invention
In view of the above-mentioned drawbacks of the prior art, the present invention provides a photoacoustic imaging contrast agent and its application, which can release Bi by employing 3+ Is used for photoacoustic diagnosis of early bacterial infection.
The invention provides a photoacoustic imaging structureA shadow agent comprising Bi 3+ And a donor.
The invention further improves that: the Bi is 3+ The donor comprises one or more of bismuth-based metal organic framework material, bismuth potassium citrate, bismuth subsalicylate, bismuth pectin.
The invention further improves that: also comprises a solvent; the solvent includes water, PBS, cell culture medium, etc.
The invention further improves that: the Bi is 3+ When the donor is bismuth-based metal organic framework material, the Bi 3+ The concentration of the donor in the photoacoustic imaging contrast agent is 0.1mg/ml to 5mg/ml.
The embodiment of the invention also comprises application of the photoacoustic imaging contrast agent in preparation of a photoacoustic probe agent for detecting bacterial infection.
The scheme provided by the invention has the following technical effects:
(1) The sensitivity is high, and early bacterial infection can be detected;
(2) Can detect various bacterial infections and has wide adaptability;
(3) The components are simple and stable, the toxicity is low, and the low-temperature preservation is not needed.
Drawings
FIG. 1 shows H production by living bacteria 2 Relevant evidence of S;
FIG. 2 is Bi 3+ Donor of (C) and H 2 S reacts and has relevant evidence of photoacoustic effect;
fig. 3 is a photoacoustic imaging result of the mouse.
Detailed Description
Other advantages and effects of the present invention will become apparent to those skilled in the art from the following disclosure, which describes the embodiments of the present invention with reference to specific examples. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention. It should be noted that the following embodiments and features in the embodiments may be combined with each other without conflict.
Embodiments of the present invention provide a photoacoustic imaging contrast agent comprising Bi 3+ A donor and a solvent. Bi (Bi) 3+ The donor comprises bismuth-based metal organic framework material (BiMOF), bismuth potassium citrate, bismuth subsalicylate, bismuth pectin, etc. can provide Bi 3+ Is a compound of (a).
In this example, the solvent is water, bi 3+ The donor used bimofs. Bi (Bi) 3+ The concentration of donor was 1mg/ml.
The principle of the photoacoustic imaging contrast agent of the present embodiment is: live bacteria will produce H 2 S molecule. As shown in FIG. 1, H was observed under the laser confocal microscope of FIG. 1 (A) 2 H expressed by bacteria in S probe (SF 7-AM, cayman Chemical, michigan, USA) 2 S activation (green fluorescence); (B) Bacteria H observed by lead acetate test paper method 2 S expression, the lead acetate test paper turns black obviously, which indicates that bacteria express H 2 S。
While at the same time Bi 3+ Can express H with bacteria 2 S to generate Bi 2 S 3 ,Bi 2 S 3 Has photoacoustic signals, thereby realizing bacterial diagnosis on the infection part.
As shown in fig. 2, the principle is illustrated by bimofs: FIG. 2. (A) a black digital photograph of BiMOF and bacteria after co-cultivation; (B) The bimofs and the products after co-cultivation of the bacteria have a photoacoustic signal, whereas the bacteria alone or the bimofs have no photoacoustic signal; (C) XRD analysis of the product after co-cultivation of BiMOF and bacteria, bi 2 S 3 The method comprises the steps of carrying out a first treatment on the surface of the (D) The segregation of Bi and S elements is obviously seen in the photographs of bacterial element distribution after co-culture of bacteria and BiMOF, and the reaction is generated between Bi and S elements.
According to the above principle, the present embodiment also includes an application of the above photoacoustic imaging contrast agent in preparing a photoacoustic probe agent for detecting bacterial infection. In this example, the bacterial infection means that H can be produced 2 S, such as Staphylococcus aureus, salmonella typhi, etc. In the photoacoustic probe reagent, the photoacoustic imaging contrast agent can be injected and infusedOr smeared on the area to be detected.
In one specific example, the experimental animals mice were divided into four groups, two normal groups and two infected groups. Infected mice were treated by injecting 200. Mu.L of the drug respectively into normal mice subcutaneously at a concentration of 10 9 The CFU/ml staphylococcus aureus realizes the molding. Two groups of mice were then injected with PBS buffer and 200. Mu.L of 1mg/ml aqueous BiMOF solution, respectively, and the photoacoustic imaging effect was observed at 0,3h,6 h.
FIG. 3 shows experimental results of subcutaneous cavity injection of PBS and 200. Mu.L lmg/ml BiMOF in normal mice or subcutaneously infected mice. Photoacoustic imaging was monitored at 0,3 and 6 hours post injection. The results show that bimofs can achieve early diagnosis of bacterial infection, forming a stronger photoacoustic signal for the staphylococcus aureus infected area.
The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (3)
1. Use of a photoacoustic imaging contrast agent in the preparation of a photoacoustic probe reagent for detecting bacterial infection; the photoacoustic imaging contrast agent comprises Bi as a component 3+ Bismuth-based metal organic framework materials for donors.
2. Use of a photoacoustic imaging contrast agent according to claim 1 for the preparation of a photoacoustic probe reagent for the detection of bacterial infections, wherein the photoacoustic imaging contrast agent further comprises a solvent; the solvent comprises water, PBS, and cell culture medium.
3. Use of a photoacoustic imaging contrast agent according to claim 2 for the preparation of a photoacoustic probe reagent for the detection of bacterial infections, characterized in that the concentration of the bismuth-based metal-organic framework material in the photoacoustic imaging contrast agent is 0.1mg/ml to 5mg/ml.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210641281.3A CN114984254B (en) | 2022-06-08 | 2022-06-08 | Photoacoustic imaging contrast agent and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202210641281.3A CN114984254B (en) | 2022-06-08 | 2022-06-08 | Photoacoustic imaging contrast agent and application thereof |
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| Publication Number | Publication Date |
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| CN114984254A CN114984254A (en) | 2022-09-02 |
| CN114984254B true CN114984254B (en) | 2023-06-27 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AUPR916101A0 (en) * | 2001-11-28 | 2001-12-20 | Bolin, Terry Dorcen | Method of treating halitosis |
| CN106754721B (en) * | 2016-11-29 | 2020-08-25 | 苏州大学 | Application of bismuth compound in preparation of autophagy initiator and autophagy model |
| CN114470235B (en) * | 2022-01-18 | 2023-05-30 | 山东大学 | Application of bismuth-based metal organic framework material as light-operated drug carrier |
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