A near-infrared fluorescence / magnetic resonance dual-mode probe and a preparation method and application thereof

Abstract

The present application relates to the technical field of nanoprobes, and particularly relates to a near-infrared fluorescence / magnetic resonance dual-mode probe and a preparation method and application thereof. The present application adopts a Brij98 amphiphilic molecule to wrap an IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule to prepare the probe, so that the probe has an absorption wavelength of 650-850 nm, generates a fluorescence signal under excitation of 785 nm laser, and the generated fluorescence wavelength can reach 1000 nm, which is in a near-infrared region (780-1700 nm); the probe has good positive magnetic resonance response characteristics, and a longitudinal relaxation rate (r1) of the probe is 28 mM ‑1 s ‑1 , which is 7 times of that of a clinically used Magnevist; the probe can be applied in the fields of fluorescence and / or magnetic resonance imaging, and has a wide application prospect. The preparation method of the near-infrared fluorescence / magnetic resonance dual-mode probe is simple in operation and low in cost.

Description

Technical Field

[0001] This invention relates to the field of nanoprobe technology, and more specifically, to a near-infrared fluorescence / magnetic resonance dual-mode probe, its preparation method, and its application. Background Technology

[0002] Medical imaging technology plays a crucial role in the early diagnosis of diseases. Molecular imaging technologies, including magnetic resonance imaging and fluorescence imaging, can image biological processes in living animals and humans at the cellular and molecular level, which is of great significance for clinical disease diagnosis.

[0003] Magnetic resonance imaging (MRI) images tissues by detecting signals generated by changes in external strong radio waves and magnetic fields acting on protons within the tissue. MRI offers numerous advantages, such as strong soft tissue resolution, flexibility in arbitrary tomographic analysis, no radiation damage, multi-parameter examination, and non-invasive, deep-penetration imaging. Therefore, MRI has become one of the most powerful techniques in clinical diagnosis today. In clinical MRI examinations, contrast-enhanced MRI with positive contrast agents is the most widely used. Positive contrast agents enhance signal intensity and improve the signal-to-noise ratio by shortening the longitudinal relaxation time (T1) of protons. Currently, clinically used positive contrast agents are mainly encapsulated in gadolinium (Gd), manganese (Mn), and iron (Fe) based contrast agents, with gadolinium-based contrast agents, such as Magnevist, Gadovist, and Eovist, being the most widely used.

[0004] Fluorescence imaging achieves its purpose by detecting the fluorescence generated when a contrast agent absorbs photons. Near-infrared fluorescence imaging has attracted widespread attention due to its advantages such as high sensitivity, high spatiotemporal resolution, non-invasiveness, and no radiation damage. In fluorescence imaging, near-infrared fluorescence (>800nm) imaging, compared to visible light fluorescence imaging (400-800nm), exhibits lower light scattering noise and autofluorescence background, enabling imaging of deep living tissues. Furthermore, the use of near-infrared contrast agents can increase the signal-to-noise ratio and sensitivity of the imaging, which is of great significance for near-infrared fluorescence imaging.

[0005] Magnetic resonance imaging (MRI) and near-infrared fluorescence imaging (NIFI), as individual imaging modalities, each have their own advantages and inherent disadvantages. MRI can achieve multi-planar tomography and deep imaging, but suffers from low resolution; NIFI can achieve high-resolution imaging, but due to limitations in light penetration depth and tissue light scattering, the imaging depth is limited to below millimeters. Multimodal imaging, which allows for the complementary advantages of different imaging modalities, represents a development trend in new imaging technologies.

[0006] Fluorescence / magnetic resonance dual-modal contrast agents can achieve fluorescence / magnetic resonance dual-modal imaging, overcoming the shortcomings of low fluorescence imaging depth and low resolution of magnetic resonance imaging technology. They organically combine the high sensitivity and high resolution of the former with the large imaging depth of the latter, enabling more realistic, accurate and comprehensive diagnostic results. This is of great significance and has a very broad application prospect.

[0007] However, existing technologies for fluorescence / magnetic resonance dual-mode imaging have limited contrast agents and probes. Publicly available quantum dots, rare earth elements, or gold nanoparticles used in this field exhibit significant toxicity and poor biocompatibility. Anthocyanin-based small-molecule organic dyes, as fluorescent dyes, have gained widespread attention in recent years due to their simple structure, easily tunable spectra, and good biocompatibility. Near-infrared fluorescent dyes emitting wavelengths in the 700–1200 nm range possess strong tissue penetration capabilities, and the weak autofluorescence of biological tissues results in low background interference and high analytical sensitivity. However, currently used small-molecule organic dyes for synthesizing fluorescence / magnetic resonance dual-mode probes primarily absorb in the visible light band. Furthermore, gadolinium-based contrast agents currently used clinically, such as Magnevist, have a low longitudinal relaxation rate (r1), leading to poor magnetic resonance imaging results. Summary of the Invention

[0008] To overcome the aforementioned technical problems, this invention provides a near-infrared fluorescence / magnetic resonance dual-mode probe, its preparation method, and its application, aiming to solve the problems of high toxicity, poor biocompatibility, absorption band in visible light, and poor magnetic resonance imaging effect of existing fluorescence / magnetic resonance dual-mode imaging contrast agents and probes.

[0009] This invention provides a near-infrared fluorescence / magnetic resonance dual-mode probe, which is a structure in which a near-infrared fluorescence / magnetic resonance dual-response molecule is encapsulated by an amphiphilic molecule. The near-infrared fluorescence / magnetic resonance dual-response molecule is used to generate a near-infrared fluorescence signal under laser excitation. The amphiphilic molecule encapsulates the near-infrared fluorescence / magnetic resonance dual-response molecule and disperses it in its hydrophobic environment.

[0010] Preferably, the near-infrared fluorescence / magnetic resonance dual-response molecule is IR824Et-PhDTA-Gd, and its chemical structural formula is as follows:

[0011]

[0012] The amphiphilic molecule is Brij98, and its chemical structural formula is as follows:

[0013]

[0014] Preferably, the mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule in the probe is 1:100.

[0015] The present invention also provides a method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe as described above, comprising the following steps:

[0016] Preparation of IR824Et-PhDTA dye;

[0017] The IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule was prepared using the IR824Et-PhDTA dye.

[0018] The probe was prepared using the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule.

[0019] Preferably, the preparation principle of the IR824Et-PhDTA dye is as follows:

[0020]

[0021] Preferably, the preparation principle of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule is as follows:

[0022]

[0023] Preferably, the probe is prepared according to the following formula:

[0024]

[0025] Preferably, the mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule to the Brij98 amphiphilic molecule is 1:100.

[0026] The present invention also provides an application of the probe described above in the fields of fluorescence and / or magnetic resonance imaging.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0028] The near-infrared fluorescence / magnetic resonance dual-mode probe of this invention, the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule, uses the IR824Et fragment as the fluorescent responsive group. This group generates a fluorescence signal after being excited by a 750-850nm laser. This wavelength is near-infrared light, which has stronger penetration ability and weaker tissue absorption and tissue light scattering effects. The PhDTA fragment can tightly complex with the magnetic resonance contrast agent Gd ions, reducing the release of Gd ions and thus reducing toxicity. The Brij98 amphiphilic molecule encapsulates the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule, dispersing it in the hydrophobic environment of the amphiphilic molecule, which can maintain the original optical properties. Moreover, the hydrophilic end of the amphiphilic molecule gives the probe good water solubility and biocompatibility.

[0029] The near-infrared fluorescence / magnetic resonance dual-mode probe of this invention has an absorption wavelength of 650-850 nm. Under 785 nm laser excitation, it generates a fluorescence signal with a wavelength reaching 1000 nm, falling within the near-infrared region (780-1700 nm). Lasers at this wavelength exhibit strong tissue penetration, and autofluorescence and light scattering in blood and tissue are weak within this band, thus providing high sensitivity and a large imaging depth. Furthermore, this probe possesses excellent positive magnetic resonance response characteristics, with a longitudinal relaxation rate (r1) of 28 mM. - 1 s -1 It is the clinically used Magnevis (r1 = 3.97 mM) -1 s -1 7 times that of ).

[0030] The preparation method of the near-infrared fluorescence / magnetic resonance dual-mode probe of the present invention is simple to operate and low in cost. The near-infrared fluorescence / magnetic resonance dual-mode probe of the present invention can be applied in the fields of fluorescence and / or magnetic resonance imaging, and has broad application prospects. Attached Figure Description

[0031] Figure 1 This is the HPLC chromatogram of the IR824Et-PhDTA dye in Example 1 of the present invention;

[0032] Figure 2 This is the normalized absorption spectrum of the IR824Et-PhDTA dye in Example 1 of the present invention;

[0033] Figure 3 The fluorescence spectrum of the IR824Et-PhDTA dye in Example 1 of this invention;

[0034] Figure 4 The normalized absorption spectrum of the IR824Et-PhDTA-Gd@Brij probe in Example 2 of this invention;

[0035] Figure 5 The fluorescence spectrum of the IR824Et-PhDTA-Gd@Brij probe under 785nm laser excitation in Example 2 of this invention;

[0036] Figure 6 This is a comparison of the fluorescence intensity of the IR824Et-PhDTA-Gd@Brij probe and ICG at a wavelength of 785nm in Example 2 of this invention.

[0037] Figure 7 This is a graph showing the longitudinal relaxation rate test results of the IR824Et-PhDTA-Gd@Brij probe in Embodiment 2 of the present invention;

[0038] Figure 8 The image shows the fluorescence stability test results of the IR824Et-PhDTA-Gd@Brij probe under 825nm laser excitation in Example 2 of this invention. Detailed Implementation

[0039] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. The following description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the embodiments of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

[0040] This invention provides a near-infrared fluorescence / magnetic resonance dual-mode probe, which is a structure in which a near-infrared fluorescence / magnetic resonance dual-response molecule is encapsulated by an amphiphilic molecule. The near-infrared fluorescence / magnetic resonance dual-response molecule is used to generate a near-infrared fluorescence signal under laser excitation. The amphiphilic molecule encapsulates the near-infrared fluorescence / magnetic resonance dual-response molecule and disperses it in its hydrophobic environment.

[0041] In a preferred embodiment, the near-infrared fluorescence / magnetic resonance dual-response molecule is IR824Et-PhDTA-Gd, and its chemical structural formula is as follows:

[0042]

[0043] The amphiphilic molecule is Brij98, and its chemical structural formula is as follows:

[0044]

[0045] In the IR824Et-PhDTA-Gd molecule, the PhDTA fragment is a polydentate ligand, capable of effectively chelating metal ions, and Gd ions can bind tightly to this fragment. The vacant coordination sites of the chelated Gd ions can bind to water molecules, altering the electron distribution of hydrogen atoms in the water molecule. This results in a difference in the NMR signal between the water molecule and the unchelated water molecule under the same magnetic field, achieving the purpose of NMR imaging.

[0046] However, the IR824Et-PhDTA-Gd molecule has poor water solubility and cannot be directly applied to organisms. Therefore, it needs to be encapsulated with amphiphilic materials to prepare a water-soluble probe, thereby increasing its biocompatibility. Brij98 is preferred as the encapsulation material. Brij98 has a hydrophobic C18 alkyl chain and a hydrophilic polyethylene glycol structure. The hydrophobic alkyl chain can encapsulate the small molecule dye, while the hydrophilic end is exposed on the outside, increasing water solubility and thus improving biocompatibility.

[0047] The preferred mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule in the probe is 1:100.

[0048] The near-infrared fluorescence / magnetic resonance dual-mode probe of this invention, the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule, uses the IR824Et fragment as the fluorescent responsive group. This group generates a fluorescence signal after being excited by a 750-850nm laser. This wavelength is near-infrared light, which has stronger penetration ability and weaker tissue absorption and tissue light scattering effects. The PhDTA fragment can tightly complex with the magnetic resonance contrast agent Gd ions, reducing the release of Gd ions and thus reducing toxicity. The Brij98 amphiphilic molecule encapsulates the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule, dispersing it in the hydrophobic environment of the amphiphilic molecule, which can maintain the original optical properties. Moreover, the hydrophilic end of the amphiphilic molecule gives the probe good water solubility and biocompatibility.

[0049] The present invention also provides a method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe as described above, comprising the following steps:

[0050] Preparation of IR824Et-PhDTA dye;

[0051] The IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule was prepared using the IR824Et-PhDTA dye.

[0052] The probe was prepared using the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule.

[0053] The preparation principle of the IR824Et-PhDTA dye is as follows:

[0054]

[0055] The preparation process of the IR824Et-PhDTA dye is as follows: starting from benzoindole 1, an imine is prepared by ethylation with iodoethane. 2; imine 2 was condensed with N-[(3-(anilinomethylene)-2-chloro-1-cyclohexen-1-yl)methylene]aniline hydrochloride 3 to prepare the near-infrared fluorescent molecule IR824Et; aminophenol 4 was deprotonated by sodium hydrogen and then reacted with IR824Et to prepare IR824Et-PhDTA precursor 5. IR824Et-PhDTA precursor 5 was deprotected by tert-butyl protecting group under the action of trifluoroacetic acid to obtain the final product IR824Et-PhDTA dye.

[0056] The preparation principle of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule is as follows:

[0057]

[0058] The preparation process of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule is as follows: after deprotonating the IR824Et-PhDTA dye under alkaline conditions, the pH of the system is adjusted, GdCl3 is added, and the mixture is stirred and mixed thoroughly at room temperature to obtain the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule solution.

[0059] The probe is prepared according to the following formula:

[0060]

[0061] The probe was prepared as follows: The solvent was removed from the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule solution by rotary evaporation; 5 mL of water was added, and the pH of the system was adjusted to approximately 12 using 0.1 M NaOH solution to obtain a suspension; the suspension was centrifuged and washed 5 times (5 mL each time) with water; the precipitate was collected, dissolved in 0.5 mL of acetonitrile, filtered through a 0.22 μm filter, and 150 μL of the filtrate was used to dissolve 150 mg of Brij98. After mixing, the solution was added dropwise to 2.85 mL of water to obtain the probe aqueous solution. The preferred mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule to the Brij98 amphiphilic molecule is 1:100.

[0062] The preparation method of the near-infrared fluorescence / magnetic resonance dual-mode probe of the present invention is simple to operate and low in cost. The near-infrared fluorescence / magnetic resonance dual-mode probe of the present invention can be applied in the fields of fluorescence and / or magnetic resonance imaging, and has broad application prospects.

[0063] The present invention also provides an application of the above-mentioned near-infrared fluorescence / magnetic resonance dual-mode probe in the fields of fluorescence and / or magnetic resonance imaging, which has broad application prospects.

[0064] Example 1

[0065] The preparation process of IR824Et-PhDTA dye is as follows:

[0066] (1) Imine Preparation of 2

[0067] Add 1.95 g of 1,1-dimethyl-1H-benzo[e]indole, a magnetic stir bar, and 50 mL of toluene to a 100 mL round-bottom flask, and set up a circulating condenser system. Heat under reflux in an oil bath overnight, then cool to room temperature, filter, and wash away impurities and toluene with diethyl ether to obtain 3.2 g of a yellow-green solid (92% yield). No further purification is required; use directly.

[0068] (2) Preparation of IR824Et

[0069] imine 2 (0.5 mmol, 182.5 mg), N-[(3-(anilinemethylene)-2-chloro-1-cyclohexen-1-yl)methylene]aniline hydrochloride 3 (0.25 mmol, 90 mg), sodium acetate (0.5 mmol, 41 mg), and a magnetic stir bar were sequentially added to a 50 mL double-necked round-bottom flask, and a circulating condenser system was set up. Air in the reaction system was replaced with argon. 10 mL of anhydrous ethanol was added, and the mixture was heated to reflux in an oil bath for 4 hours. After cooling to room temperature, the anhydrous ethanol was removed by rotary evaporation, and 140 mg of the green solid IR824Et was obtained by silica gel column chromatography, with a yield of 76%. The 1H NMR spectrum of the green solid IR824Et is as follows: NMR (400MHz, MeOD) δ 8.59 (d, J = 14.3Hz, 2H), 8.30 (d, J = 8.5Hz, 2H), 8.07 (d, J = 8.8Hz, 2H), 8.03 (d, J = 8.2Hz, 2H), 7.71–7.63 (m, 4H), 7.56–7.50 (m, 2H), 6.37 (d, J = 14.2Hz, 2H), 4.38 (q, J = 7.2Hz, 4H), 2.81 (t, J = 6.1Hz, 4H), 2.07–2.01 (m, 14H), 1.51 (t, J = 7.2Hz, 6H). High-resolution mass spectrometry data for the green solid IR824Et are: HRMS (MALDI-TOF) m / z: [MI] + calcd for C 42 H 44 ClN2 + :611.312;Found:611.271;

[0070] (3) Preparation of IR824Et-PhDTA precursor 5

[0071] NaH (containing 40% mineral oil stabilizer, 27 mg, 0.68 mmol) and a magnetic stir bar were placed in a 100 mL round-bottom flask. Under an argon atmosphere, 10 mL of anhydrous DMF was added, and the mixture was cooled in an ice-water bath. A solution of aminophenol 4 (361 mg, 0.62 mmol) dissolved in 15 mL of anhydrous DMF was slowly added dropwise to the NaH suspension, and the reaction was allowed to proceed at room temperature for half an hour. The reaction system was then withdrawn using a syringe and, under an argon atmosphere, slowly added to a solution of IR824Et (382 mg, 0.51 mmol) in 25 mL of anhydrous DMF. The mixture was stirred at room temperature for 3 hours. The flask was placed in an ice-water bath, and the reaction was quenched with water. The mixture was extracted three times with dichloromethane, and the organic phases were combined. The mixture was dried over anhydrous Na2SO4, and the organic solvent was removed by rotary evaporation. 381 mg of the green solid IR824Et-PhDTA precursor 5 was obtained by silica gel column chromatography, with a yield of 58%. The 1H NMR data for the green solid IR824Et-PhDTA precursor 5 are as follows: NMR(400MHz,MeOD)δ8.20-8.10(m,4H),8.02-7.96(m,4H),7.65-7.52(m,4H) ,7.50-7.43(m,2H),7.16(d,J=9.4Hz,1H),6.84-6.76(m,2H),6.19(d,J=14.3 Hz,2H),4.32-4.20(m,8H),4.08(s,4H),2.80(t,J=5.8Hz,4H),2.11(quin,J= 5.8Hz, 2H), 1.44 (t, J = 7.1Hz, 6H), 1.37 (s, 18H), 1.26 (s, 18H), 1.22 (s, 12H).

[0072] (4) Preparation of IR824Et-PhDTA dye

[0073] IR824Et-PhDTA precursor 5 (381 mg, 0.30 mmol) and a magnetic stir bar were placed in a 25 mL round-bottom flask, and 5 mL of trifluoroacetic acid was added. The mixture was stirred at room temperature for 4 hours. Trifluoroacetic acid was removed by rotary evaporation, and the mixture was then separated by HPLC (C18 reversed-phase column, mobile phase: 15% water and 85% methanol, flow rate: 1 mL / min, retention time: 18 min). Figure 1(As shown) 240 mg of IR824Et-PhDTA dye was obtained, with a yield of 76%. The 1H NMR data for IR824Et-PhDTA dye are as follows: 1H NMR (400 MHz, MeOD) δ 8.26 (d, J = 8.5 Hz, 2H), 8.12 (d, J = 14.3 Hz, 2H), 8.02–7.92 (m, 4H), 7.65–7.59 (m, 2H), 7.54 (d, J = 8.8 Hz, 2H), 7.50–7.42 (m, 2H), 7.11 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 2.7 Hz, 1H), 6.54 (dd, J1 = 2.7 Hz, J2 = 8.8 Hz). 1H), 6.16 (d, J = 14.3Hz, 2H), 4.51 (s, 4H), 4.30-4.18 (m, 8H), 2.78 (t, J = 5.6Hz, 4H), 2.08 (quin, J = 5.6Hz, 2H), 1.65 (s, 12H), 1.42 (t, J = 7.1Hz, 6H).

[0074] like Figure 2 The normalized absorption spectrum of the IR824Et-PhDTA dye prepared in this embodiment is shown. It can be seen that the maximum absorption peak of the IR824Et-PhDTA dye in methanol is 803 nm, and the absorption peak is located in the near-infrared region (780-1700 nm). Under corresponding near-infrared laser irradiation, the molecule transitions from the ground state to an excited state, and then releases energy in the form of light and heat to return to the ground state. The portion of energy released in the form of light produces fluorescence. The fluorescence spectrum of the IR824Et-PhDTA dye in methanol is shown below. Figure 3 As shown.

[0075] Example 2

[0076] The fabrication process of the IR824Et-PhDTA-Gd@Brij near-infrared fluorescence / magnetic resonance dual-mode probe is as follows:

[0077] Add 5 mg of the IR824Et-PhDTA dye prepared in Example 1 and 2.5 mL of water to a 25 mL round-bottom flask. Add 0.1 M NaOH solution dropwise until the solution becomes clear, at which point the pH is approximately 12. Adjust the pH of the system to approximately 7 with 0.1 M hydrochloric acid, and add 2.5 mL of methanol. Add 0.5 mL of GdCl3 aqueous solution (5 mg / mL) and stir overnight at room temperature. Remove the solvent by rotary evaporation. Add 5 mL of water and adjust the pH of the system to approximately 12 with 0.1 M NaOH solution to obtain a suspension. Centrifuge and wash with water 5 times (5 mL / time). Collect the precipitate, dissolve it in 0.5 mL of acetonitrile, filter through a 0.22 μm filter, take 150 μL to dissolve 150 mg of Brij, mix well, and add dropwise to 2.85 mL of water to obtain the probe aqueous solution. The molar ratio of IR824Et-PhDTA dye to GdCl3 is 1:3, and the mass ratio of IR824Et-PhDTA-Gd molecules to Brij98 is 1:100. The binding rate of IR824Et-PhDTA dye to Gd ions is 83% (calculated from the Gd concentration measured by ICP).

[0078] like Figure 4 The image shows the normalized absorption spectrum of the IR824Et-PhDTA-Gd@Brij probe prepared in this embodiment. It can be seen that the maximum absorption peak of the IR824Et-PhDTA-Gd@Brij probe is 817 nm, and the absorption peak range is 650-850 nm. Figure 5 The image shows the fluorescence spectrum of the IR824Et-PhDTA-Gd@Brij probe prepared in this embodiment under 785nm laser excitation. It can be seen that the maximum emission peak wavelength of the IR824Et-PhDTA-Gd@Brij probe is 824nm, and the emission peak range can reach 1000nm. Figure 6 The image shows a comparison of the fluorescence intensity of the IR824Et-PhDTA-Gd@Brij probe prepared in this embodiment and ICG at a wavelength of 785 nm. It can be seen that, at the same absorption intensity, the fluorescence intensity of the IR824Et-PhDTA-Gd@Brij probe aqueous solution is stronger than that of the commercially available fluorescent reagent ICG. Figure 7 The figure shown is a graph of the longitudinal relaxation rate test results of the IR824Et-PhDTA-Gd@Brij probe prepared in this embodiment. It can be seen that the longitudinal relaxation rate (r1) of the IR824Et-PhDTA-Gd@Brij probe is 28 mM. -1 s -1 This is significantly higher than that of the commercially available reagent Magnevist (r1 = 3.97 mM). -1 s -1 ). Figure 8The image shows the fluorescence stability test results of the IR824Et-PhDTA-Gd@Brij probe prepared in this embodiment under 825nm laser excitation. The sample was stored at room temperature. It can be seen that the fluorescence of the IR824Et-PhDTA-Gd@Brij probe has a certain stability. The fluorescence intensity on the third day is about 64% of the fluorescence intensity on the first day.

[0079] The near-infrared fluorescence / magnetic resonance dual-mode probe of this invention has an absorption wavelength of 650-850 nm. Under 785 nm laser excitation, it generates a fluorescence signal with a wavelength reaching 1000 nm, falling within the near-infrared region (780-1700 nm). Lasers at this wavelength exhibit strong tissue penetration, and autofluorescence and light scattering in blood and tissue are weak within this band, thus providing high sensitivity and a large imaging depth. Furthermore, this probe possesses excellent positive magnetic resonance response characteristics, with a longitudinal relaxation rate (r1) of 28 mM. - 1 s -1 It is the clinically used Magnevis (r1 = 3.97 mM) -1 s -1 7 times that of ).

[0080] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A near-infrared fluorescence / magnetic resonance dual-mode probe, characterized in that, The structure comprises an amphiphilic molecule encapsulating a near-infrared fluorescence / magnetic resonance dual-response molecule, wherein the near-infrared fluorescence / magnetic resonance dual-response molecule is used to generate a near-infrared fluorescence signal under laser excitation, and the amphiphilic molecule encapsulates and disperses the near-infrared fluorescence / magnetic resonance dual-response molecule in its hydrophobic environment; wherein: The near-infrared fluorescence / magnetic resonance dual-response molecule is IR824Et-PhDTA-Gd, and its chemical structure is as follows: The amphiphilic molecule is Brij98.

2. The near-infrared fluorescence / magnetic resonance dual-mode probe according to claim 1, characterized in that: The mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule in the probe is 1:

100.

3. A method for preparing a near-infrared fluorescence / magnetic resonance dual-mode probe as described in claim 1, characterized in that, Includes the following steps: Preparation of IR824Et-PhDTA dye; The IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule was prepared using the IR824Et-PhDTA dye. The probe was prepared using the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule and the Brij98 amphiphilic molecule.

4. The method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe according to claim 3, characterized in that, The preparation principle of the IR824Et-PhDTA dye is as follows:

5. The method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe according to claim 3, characterized in that, The preparation principle of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule is as follows:

6. The method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe according to claim 3, characterized in that, The probe is prepared according to the following formula:

7. The method for preparing the near-infrared fluorescence / magnetic resonance dual-mode probe according to claim 3, characterized in that, The mass ratio of the IR824Et-PhDTA-Gd near-infrared fluorescence / magnetic resonance dual-response molecule to the Brij98 amphiphilic molecule is 1:100.

Images