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A nano-therapeutic material that crosses the blood-brain barrier and targets orthotopic glioma and its preparation method

A nanomaterial and nanocrystal technology, applied in nanodiagnostic agent materials and preparation thereof, transferrin-based nanomaterials and preparation thereof, and preparation of nanodiagnostic agents that efficiently cross the blood-brain barrier and target glioma in situ. Application field, achieve the effect of avoiding post-modification targeting molecular steps, simple reaction and good dispersibility

Active Publication Date: 2021-08-06
SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, few studies have been able to transport MnO through the BBB 2 to achieve MRI of the glioma region, because it is difficult to endow MnO with traditional post-modification methods 2 Ability to penetrate the BBB while modulating its size

Method used

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  • A nano-therapeutic material that crosses the blood-brain barrier and targets orthotopic glioma and its preparation method
  • A nano-therapeutic material that crosses the blood-brain barrier and targets orthotopic glioma and its preparation method
  • A nano-therapeutic material that crosses the blood-brain barrier and targets orthotopic glioma and its preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Weigh 60 mg of iron-saturated transferrin (holo-transferrin, holo-Tf) and dissolve it in 30 mL of distilled water, add 0.2 mL of 0.1 M manganese chloride aqueous solution, and stir for 15 min. Then slowly add 0.36mL of 0.1M NaOH aqueous solution dropwise, while monitoring the pH change of the solution during the dropping process with a pH meter, so that the peak value of the pH of the solution does not exceed 8.4. Continue to stir for 0.5-1h after the dropwise addition. The obtained material was filtered with a 220 μm microporous filter, and then dialyzed in distilled water for 24-36h (dialysis bag molecular weight cut-off 3000) to obtain MnO 2 @Tf(TM) nanomaterials.

[0058] Dissolve 3 mg protoporphyrin (ppIX), 3 mg N-hydroxysuccinimide (NHS), 1.8 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) In DMF solution (1ml), avoid light and mix and stir for 1-2h to activate the carboxyl group in protoporphyrin. Add the activated solution to the prepared...

Embodiment 2

[0060] Weigh 60 mg of iron-saturated transferrin (holo-transferrin, holo-Tf) and dissolve it in 30 mL of distilled water, add 0.5 mL of 0.1 M manganese chloride aqueous solution, and stir for 15 min. Then slowly drop into 0.9mL of 0.1M NaOH aqueous solution, and monitor the pH change of the solution during the dropping process with a pH meter at the same time, so that the peak value of the solution pH does not exceed 8.4. Continue to stir for 0.5-1h after the dropwise addition. The obtained material was filtered with a 220 μm microporous filter, and then dialyzed in distilled water for 24-36h (dialysis bag molecular weight cut-off 3000) to obtain MnO 2@Tf(TM) nanomaterials.

[0061] Dissolve 3 mg protoporphyrin (ppIX), 3 mg N-hydroxysuccinimide (NHS), 1.8 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) In DMF solution (1ml), avoid light and mix and stir for 1-2h to activate the carboxyl group in protoporphyrin. Add the activated solution to the prepared...

Embodiment 3

[0063] Weigh 60 mg of iron-saturated transferrin (holo-transferrin, holo-Tf) and dissolve it in 30 mL of distilled water, add 1 mL of 0.1 M manganese chloride aqueous solution, and stir for 15 min. Then slowly drop into 1.8mL of 0.1M NaOH aqueous solution, and monitor the pH change of the solution during the dropping process with a pH meter at the same time, so that the peak value of the solution pH does not exceed 8.4. Continue to stir for 0.5-1h after the dropwise addition. The obtained material was filtered with a 220 μm microporous filter, and then dialyzed in distilled water for 24-36h (dialysis bag molecular weight cut-off 3000) to obtain MnO 2 @Tf(TM) nanomaterials.

[0064] Dissolve 3 mg protoporphyrin (ppIX), 3 mg N-hydroxysuccinimide (NHS), 1.8 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) In DMF solution (1ml), avoid light and mix and stir for 1-2h to activate the carboxyl group in protoporphyrin. Add the activated solution to the prepared ...

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Abstract

The invention relates to a nano-diagnosis and treatment agent material and a preparation method thereof that can efficiently cross the blood-brain barrier and target in situ brain gliomas, in particular to a transferrin-based nano-material and a preparation method thereof and in the preparation of high-efficiency cross-blood-brain barrier materials. Barrier and targeting in situ brain glioma nano-therapeutics; the transferrin-based nanomaterials include: iron-saturated transferrin holo-Tf as a carrier, and MnO loaded in the carrier 2 nanocrystals and protoporphyrin; and the MnO 2 Nanocrystals and protoporphyrin molecules are co-packed in transferrin to form a core-shell structure.

Description

technical field [0001] The invention relates to a nano-diagnosis and treatment agent material and a preparation method thereof that can efficiently cross the blood-brain barrier and target in situ brain gliomas, in particular to a transferrin-based nano-material and a preparation method thereof and in the preparation of high-efficiency cross-blood-brain barrier materials. The application of the barrier and targeting in situ glioma nano-diagnosis and treatment agent belongs to the field of nano-medicine. Background technique [0002] Malignant glioma (GBM), as a malignant brain tumor, is characterized by poor prognosis, invasive growth, high recurrence and mortality rates, and a poor median survival time of only 14.6 months. This can be largely attributed to the existence of the blood-brain-barrier (BBB), which seriously hinders the successful delivery of drugs, MR contrast agents and other substances to the brain, thereby greatly impairing the effectiveness of diagnosis and ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/14A61K49/18A61K9/51A61K41/00A61P35/00A61P25/00
CPCA61K9/5169A61K41/0033A61K49/14A61K49/1818A61P25/00A61P35/00
Inventor 陈航榕梁凯程罗宇张秋红
Owner SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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