An iodine-125 labeled iron-based nanomaterial and its use

Abstract

The present invention belongs to the technical field of tumor treatment drug research, and specifically relates to an iodine-125 labeled iron-based nanomaterial and its use. The iron-based nanomaterial is obtained by labeling a metal-organic framework material of iron with a radionuclide 125 I. When in use, the iron-based nanomaterial provided by the present invention can continuously generate hydrated electrons (e aq ‑ ) for a long time by using radioactive iodine 125. e aq ‑ promotes the conversion of transition metals from high valence states to low valence states, improves the Fenton reaction efficiency at the tumor site, and the anti-tumor efficacy of chemodynamic therapy.

Description

Technical Field

[0001] The invention belongs to the technical field of tumor therapeutic drug research, and specifically relates to an iodine-125 labeled iron-based nanomaterial and a use thereof. Background Art

[0002] Chemodynamic therapy is a new type of tumor treatment technology that uses the acidic nature of the tumor microenvironment and H 2 O 2 The characteristics of high expression of transition metal nanomaterials such as iron can be introduced into the tumor to activate the Fenton / Fenton-like reaction in situ, generating hydroxyl free radicals with strong oxidative properties, thereby killing tumor cells. However, taking iron-based nanomaterials as an example, due to the Fe 3+ / Fe 2+ The existence of the conversion rate-limiting step leads to low efficiency of the Fenton reaction, which seriously restricts the therapeutic effect of chemical kinetics. 3+ Fe 2+ The conversion is of great significance to increasing the efficiency of intracellular Fenton reactions and improving chemical kinetics.

[0003] Promoting the high-to-low valence conversion of transition metals is an important means to enhance the therapeutic effect of CDT on tumors. Existing technologies mainly use reducing agents such as GSH in the tumor microenvironment to reduce metals in high valence states. However, due to the limited amount of reducing substances such as GSH and the difficulty in controlling them, the enhancement of CDT efficacy is not ideal. Therefore, how to efficiently and continuously convert high-valence transition metals into low-valence states is a key scientific issue in improving the efficacy of CDT. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention provides an iodine-125 labeled iron-based nanomaterial, which can utilize radioactive iodine-125 to continuously generate hydrated electrons (e aq - ), e aq - Promote the conversion of transition metals from high-valent states to low-valent states, improve the efficiency of Fenton reaction in tumor sites, and enhance the anti-tumor efficacy of chemodynamic therapy.

[0005] The specific technical solutions provided by the present invention are as follows:

[0006] The present invention provides an iodine-125 labeled iron-based nanomaterial, which utilizes radioactive nuclides 125 I was obtained after labeling the iron-based metal-organic framework material.

[0007] Preferably, the particle size of the iron-based nanomaterial is 80-120 nm.

[0008] Preferably, the radionuclide 125I labeling was performed using the iodogen method.

[0009] Preferably, the radionuclide 125 I marking is carried out according to the following steps:

[0010] Will 125 The I-NaI solution is mixed with Iodogen, and a solution of the iron-based metal-organic framework material is added, shaken, and centrifuged. The resulting precipitate is the iron-based nanomaterial labeled with iodine-125.

[0011] Preferably, the 125 The concentration of I-NaI solution is 10 mCi. 125 The usage ratio of I-NaI solution to Iodogen is 2-10 μL: 5-50 μg.

[0012] Preferably, the 125 The volume ratio of the I-NaI solution to the iron-based metal-organic framework nanomaterial solution is 1:5, and the mass concentration of the iron-based metal-organic framework nanomaterial solution is 1.0 mg / mL.

[0013] Preferably, the shaking is performed at room temperature for 10 minutes, and the centrifugation is performed at 13000 r / min for 5 minutes.

[0014] Preferably, the iron-based metal-organic framework nanomaterial is MIL-88B (Fe).

[0015] Preferably, the MIL-88B(Fe) is prepared according to the following steps:

[0016] The metal-organic framework nanomaterial OH-MIL-88B(Fe) was synthesized using o-hydroxyterephthalic acid as an organic ligand and trivalent iron salt as an iron source.

[0017] OH-MIL-88B(Fe) and polyethylene glycol are mixed and stirred, and centrifuged to obtain the precipitate, which is MIL-88B(Fe).

[0018] Preferably, o-hydroxyterephthalic acid is prepared into solutions with a concentration of 2 to 8 M and the trivalent iron source is prepared into solutions with a concentration of 3 to 12 M, and the solutions are mixed and reacted.

[0019] Preferably, the process of synthesizing the metal-organic framework nanomaterial OH-MIL-88B (Fe) is to use ethanol as a solvent and react at 50 to 80° C. for 4 to 24 hours.

[0020] Preferably, the molecular weight of the polyethylene glycol is 2000-10000, and the mass ratio of OH-MIL-88B(Fe) to polyvinyl alcohol is 1:5-20.

[0021] Preferably, the stirring time is 4 to 24 hours, and the centrifugation is performed at 5000 to 13000 r / min to remove free polyethylene glycol.

[0022] The present invention also provides a use of the iron-based nanomaterial in preparing anti-tumor drugs.

[0023] Compared with the prior art, the beneficial effects of the present invention are:

[0024] 1. The present invention utilizes radionuclides 125 I-labeled iron-based metal-organic framework (MOF) nanomaterial MIL-88B (Fe) was used to synthesize a new CDT agent. On the one hand, the pore structure of MOF is conducive to the H 2 O 2 The enrichment, on the other hand 125 I The hydration electrons (e aq - ) can efficiently achieve Fe 3+ / Fe 2+ conversion, greatly improving the efficiency of the iron-based Fenton reaction.

[0025] 2. The present invention utilizes the decay of radioactive nuclides and the interaction with surrounding water to continuously generate a large amount of e aq - , thereby providing a continuous and stable electron donor, directly realizing the high-to-low valence state conversion of transition metals, improving the efficiency of the Fenton reaction, and thus enhancing the efficacy of CDT.

[0026] 2. Experiments on pancreatic cancer cells and tumor-bearing mice showed that the 125 I-MIL-88B(Fe) can enhance the efficacy of CDT, and the ROS / MAPK / p53 signaling pathway plays an important role in it. The present invention not only provides a new research idea for achieving efficient CDT, but also expands the application of radionuclides. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 yes 125 Flowchart of the synthesis of I-MIL-88B(Fe).

[0028] Figure 2 This is a transmission electron microscope (TEM) image of the material OH-MIL-88B(Fe).

[0029] Figure 3 It is the X-ray diffraction pattern (XRD) of material OH-MIL-88B(Fe).

[0030] Figure 4 This is the infrared spectrum of polyethylene glycol modified material MIL-88B(Fe).

[0031] Figure 5 yes 125 Radioactive thin layer chromatogram of I-MIL-88B(Fe).

[0032] Figure 6 It is the UV absorption spectrum of dye R240.

[0033] Figure 7 This is the UV absorption spectrum of o-phenanthroline.

[0034] Figure 8 It is the electron spin resonance spectroscopy (ESR).

[0035] Fig. 9 yes 125 Effects of I-MIL-88B(Fe) on cells: a) Confocal microscopy to detect intracellular hydroxyl radicals, b) Confocal microscopy to assess cell survival.

[0036] Fig.10 yes 125 Anti-tumor performance of I-MIL-88B(Fe) in small animal tumor-bearing mouse model: a) 125 I-MIL-88B(Fe) can stay in the tumor area for a long time, b) tumor size growth curve of tumor-bearing mice, c) weight of ex vivo tumor after 14 days of treatment. DETAILED DESCRIPTION

[0037] The present invention will be further described below in conjunction with specific embodiments. The following embodiments are only used to illustrate the present invention and are not intended to limit the scope of application of the present invention. Without departing from the spirit and essence of the present invention, modifications or replacements made to the inventive method, steps or conditions all belong to the scope of the present invention.

[0038] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the materials and reagents used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0039] Example 1

[0040] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0041] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0042] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0043] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0044] Example 2

[0045] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe) is prepared according to the following steps:

[0046] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0047] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0048] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 5 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to shake slightly at room temperature for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0049] Example 3

[0050] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0051] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0052] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0053] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (10 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) physiological saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was gently shaken at room temperature for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper liquid was discarded, and the precipitate was retained. The precipitate was dispersed in physiological saline again to obtain 125 I-MIL-88B(Fe) solution.

[0054] Example 4

[0055] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1As shown, it is prepared according to the following steps:

[0056] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0057] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0058] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (10 μL) was then added to an Eppendorf tube coated with 5 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) physiological saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was gently shaken at room temperature for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper liquid was discarded, and the precipitate was retained. The precipitate was dispersed in physiological saline again to obtain 125 I-MIL-88B(Fe) solution.

[0059] Example 5

[0060] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0061] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration of 8M, FeCl 3 The metal iron source was 12 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0062] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0063] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0064] Example 6

[0065] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0066] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration of 5M, FeCl 3 The metal iron source was 8 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0067] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0068] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0069] Example 7

[0070] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0071] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 80 °C, and the reaction time was 24 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0072] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0073] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0074] Example 8

[0075] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1As shown, it is prepared according to the following steps:

[0076] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 80 °C, and the reaction time was 4 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0077] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0078] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0079] Example 9

[0080] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0081] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0082] S2. Add polyethylene glycol 10000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:5, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0083] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0084] Example 10

[0085] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0086] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0087] S2. Add polyethylene glycol 2000 to the OH-MIL-88B(Fe) solution at a mass ratio of 1:20 between OH-MIL-88B(Fe) and polyethylene glycol, and stir for 24 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0088] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was allowed to react at room temperature with slight shaking for 10 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper layer of liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0089] Embodiment 11

[0090] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1 As shown, it is prepared according to the following steps:

[0091] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0092] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 4 hours. Then centrifuge at 13000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0093] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was gently shaken at room temperature for 5 minutes, the solution was aspirated, and centrifuged at 5000 r / min for 15 minutes, the upper liquid was discarded, and the precipitate was retained. The precipitate was dispersed in saline again to obtain 125 I-MIL-88B(Fe) solution.

[0094] Example 12

[0095] An iodine-125 labeled iron-based nanomaterial, labeled 125 I-MIL-88B(Fe), such as Figure 1As shown, it is prepared according to the following steps:

[0096] S1, o-hydroxyterephthalic acid (HTPA) as organic ligand, concentration is 2M, FeCl 3 The metal iron source was 3 M in concentration, ethanol was used as solvent, the temperature was controlled at 55 °C, and the reaction time was 12 h to synthesize the metal-organic framework (MOF) nanomaterial OH-MIL-88B (Fe).

[0097] S2. Add polyethylene glycol 4000 to the OH-MIL-88B(Fe) solution with a mass ratio of OH-MIL-88B(Fe) to polyethylene glycol of 1:10, and stir for 24 hours. Then centrifuge at 5000 r / min for 10 minutes to remove free polyethylene glycol. The precipitate is PEG@OH-MIL-88B(Fe) (abbreviated as MIL-88B(Fe)).

[0098] S3. Radioactivity using the classic Iodogen method 125 I label. Take 10mCi 125 I-NaI solution (20 μL) was then added to an Eppendorf tube coated with 50 μg of Iodogen at the bottom, and then 100 μL of LMI-88B (Fe) physiological saline solution (Fe concentration: 1.0 mg / mL) was added. The reaction was gently shaken at room temperature for 15 minutes, the solution was aspirated, and centrifuged at 13000 r / min for 5 minutes, the upper liquid was discarded, and the precipitate was retained. The precipitate was dispersed in physiological saline again to obtain 125 I-MIL-88B(Fe) solution.

[0099] Since the 125 The performance of I-MIL-88B(Fe) is basically the same, so the following only takes Example 1 as an example to illustrate its performance and application effect.

[0100] 1. 125 Characterization of I-MIL-88B(Fe)

[0101] 1) Take 20 μL of the prepared MIL-88B (Fe) solution and drop it onto the carbon film copper grid, let it dry naturally, and send the inspection material to a transmission electron microscope (TEM).

[0102] 2) Take 5 mL of MIL-88B(Fe) solution, centrifuge and freeze-dry, and send the sample for XRD testing.

[0103] 3) Take 2 mg of freeze-dried sample, PEG and OH-MIL-88B(Fe), press them into tablets with potassium bromide, and send them for infrared spectrum (IR) measurement.

[0104] 4) Take 10 μL125 I-MIL-88B(Fe) was dropped onto chromatographic paper tape, developed with water, and detected by radioactive thin layer chromatography.

[0105] 2. Experimental results

[0106] like Figure 2 As shown, 125 The size of I-MIL-88B(Fe) is about 100nm. The X-ray diffraction pattern (XRD) of the material shows that the material is an iron-grade MOF with MIL-88B structure ( Figure 3 ), infrared spectrum shows that the material was successfully modified by PEG ( Figure 4 ), radioactive thin layer chromatography results ( Figure 5 ) indicates that radioactive iodine 125 can be stably labeled on the material. 125 I-MIL-88B(Fe) was successfully obtained.

[0107] Experimental Example 1

[0108] 125 I-MIL-88B(Fe) uses iodine-125 to release hydrated electrons to improve the efficiency of Fenton reaction

[0109] 1. Experimental methods

[0110] 1) Take 0.2 mL 125 The I-MIL-88B(Fe) solution was centrifuged and diluted to 2 mL of solution, followed by the addition of 25 μg of RR240 dye and the solution was transferred to a 2-way cuvette to detect the UV absorption spectrum of the solution.

[0111] 2) Take 0.2 mL 125 The I-MIL-88B (Fe) solution was centrifuged and diluted to 2 mL of solution, followed by the addition of 25 μg of o-phenanthroline (Phen) dye, and the solution was transferred to a 2-way cuvette to detect the UV absorption spectrum of the solution.

[0112] 3) Take 0.5mL of pH 6.5 and 7.4 respectively 125 I-MIL-88B(Fe) solution and MIL-88B(Fe), followed by the addition of a hydroxyl radical scavenger (DMPO) and 1 mM hydrogen peroxide, and the electromagnetic paramagnetic resonance spectrum of the solution was detected.

[0113] 2. Experimental results

[0114] like Figure 6 As shown in Figure 2, the UV absorption spectrum of dye R240 increases with time, the UV-visible absorption increases in the wavelength range of 250-350nm, and decreases in the wavelength range of 400-550nm, proving that 125Iodine 125 on I-MIL-88B(Fe) can generate hydrated electrons.

[0115] Figure 7 This is the UV absorption spectrum of o-phenanthroline. As time goes by, the UV-visible absorption increases at 400-600nm, proving that 125 I-MIL-88B(Fe) generates hydrated electrons that can convert Fe 3+ Converted to Fe 2+ .

[0116] Figure 8 The electron spin resonance spectrum (ESR) shows a characteristic peak of hydroxyl radicals in the range of 1:2:2:1 in the range of 3450-3550G, and 125 The signal of group I-MIL-88B(Fe) was the strongest, proving 125 I-MIL-88B(Fe) can catalyze the decomposition of hydrogen peroxide to produce more hydroxyl radicals.

[0117] Example 3: In a simulated environment 125 I-MIL-88B(Fe) can produce more hydroxyl free radicals in cells and effectively kill pancreatic cancer cells

[0118] 1. Experimental methods

[0119] Pancreatic cancer cells Panc-1 (1×10 5 ) were inoculated into 8 confocal dishes and cultured for 24 h. Subsequently, different treatments were used: (G1) control group (DMEM only), (G2) MIL-88B(Fe), (G3) 125I-MIL-88B(Fe), (G4) H 2 O 2 , (G5)H 2 O 2 +MIL-88B(Fe)(pH 7.4),(G6)H 2 O 2 +125I-MIL-88B(Fe)(pH 7.4), (G7)H 2 O 2 +MIL-88B(Fe)(pH 6.5),(G8)H 2 O 2 +125I-MIL-88B(Fe), incubate for 24h. Stain the cells with 1mL 0.2μMAPF hydroxyl radical probe and 1mL 0.2μM calcein-AM / propidium iodide staining reagent and incubate for 30min. Finally, observe the cell staining results with a confocal fluorescence microscope.

[0120] 2. Experimental results

[0121] like Fig. 9 a is the staining of intracellular hydroxyl free radicals. 125 The green fluorescence of group I-MIL-88B(Fe) was the strongest, proving 125 I-MIL-88B(Fe) can catalyze the decomposition of intracellular hydrogen peroxide and produce more hydroxyl free radicals. Fig. 9 b is the result of cell death and viability staining. 125 The green fluorescence (representing living cells) of the I-MIL-88B(Fe) group was weak and the red fluorescence (representing dead cells) was the strongest, proving that 125 I-MIL-88B(Fe) produces more hydroxyl radicals and can kill tumor cells more efficiently.

[0122] Experimental Example 3

[0123] 125 Therapeutic Effect of I-MIL-88B(Fe) on Pancreatic Cancer-bearing Mice

[0124] 1. Experimental methods

[0125] In a panc-1 tumor-bearing mouse model, we studied 125 I-MIL-88B(Fe) anti-tumor therapeutic effect. To evaluate the tumor inhibitory effect, panc-1 tumor-bearing nude mice were randomly divided into 4 groups: (1) control group, (2) MIL-88B(Fe) group, (3) 125 I-SiO 2 Group, (4) 125 I-MIL-88B(Fe) group. Intratumoral administration was as follows Figure 4 As shown, the body weight and tumor volume of mice were observed for 14 days. On the 14th day, the mice were killed, and the tumors were removed, weighed, and the volume was measured.

[0126] 2. Experimental results

[0127] like Fig.10 As shown in a, 125 I-MIL-88B(Fe) nanomaterials can stay in the tumor site for a long time. Compared with other groups, 125 Tumor growth was inhibited in mice treated with I-MIL-88B(Fe) ( Fig.10 b), and the tumor weight is also the lightest ( Fig.10 c) Description 125 I-MIL-88B(Fe) can improve the efficiency of Fenton reaction and thus enhance the efficacy of CDT by providing a continuous and stable electron donor.

[0128] The above embodiments are used to illustrate the present invention rather than to limit the present invention. Any modification and change made to the present invention within the spirit of the present invention and the protection scope of the claims shall fall within the protection scope of the present invention.

Claims

1. An iodine-125 labeled iron-based nanomaterial, characterized in that: It uses radionuclides 125 I is used to label the iron-based metal-organic framework material, and the radionuclide 125 I is used to continuously generate hydrated electrons by radiolysis of water to achieve high-low valence state conversion of transition metals and improve the efficiency of Fenton reaction; the iron-based metal-organic framework material is MIL-88B (Fe), and the particle size of the iron-based nanomaterial is 80-120 nm.

2. The iron-based nanomaterial according to claim 1, characterized in that: Radionuclides 125 I marking is carried out in the following steps: Will 125 The I-NaI solution is mixed with Iodogen, and a solution of the iron-based metal organic framework material is added, shaken, and centrifuged. The resulting precipitate is the iron-based nanomaterial labeled with iodine-125.

3. The iron-based nanomaterial according to claim 2, characterized in that: Said 125 The concentration of I-NaI solution is 10 mCi. 125 The dosage ratio of I-NaI solution to Iodogen is 2~10 μL: 5~50 μg.

4. The iron-based nanomaterial according to claim 3, characterized in that: Said 125 The volume ratio of the I-NaI solution to the iron-based metal-organic framework material solution is 1:5-10, and the mass concentration of the iron-based metal-organic framework material solution is 1.0 mg / mL.

5. The iron-based nanomaterial according to claim 1, characterized in that: The MIL-88B(Fe) is prepared according to the following steps: The metal-organic framework nanomaterial OH-MIL-88B(Fe) was synthesized using o-hydroxyterephthalic acid as an organic ligand and trivalent iron salt as an iron source. OH-MIL-88B(Fe) and polyethylene glycol are mixed and stirred, and centrifuged to obtain the precipitate, which is MIL-88B(Fe).

6. The iron-based nanomaterial according to claim 5, characterized in that: The o-hydroxyterephthalic acid and the trivalent iron source are prepared into solutions with a concentration of 2-8M and 3-12M, respectively, and the solutions are mixed and reacted at 50-80°C.

7. The iron-based nanomaterial according to claim 5, characterized in that: The molecular weight of the polyethylene glycol is 2000-10000, and the mass ratio of OH-MIL-88B (Fe) to polyvinyl alcohol is 1:5-20.

8. Use of the iron-based nanomaterial according to any one of claims 1 to 7 in the preparation of anti-tumor drugs, characterized in that: The tumor is pancreatic cancer.

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