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Ammoniaborane/hollow mesoporous polydopamine/polyethylene glycol nanocomposite particles and its preparation and application

A technology of nanocomposite particles and polydopamine, which is applied in the direction of active ingredients of boron compounds, drug combinations, and medical preparations of non-active ingredients, etc., which can solve the problem of inability to exert high permeability and retention effect efficiently, and limited loading capacity of polydopamine , lack of problems such as inhibiting tumor metastasis, achieving high drug loading efficiency, shortening the preparation cycle, and improving the effect of treatment

Active Publication Date: 2022-04-12
EAST CHINA NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the technical solution of this patent has the following technical problems: 1. The particle size of the MnCO@MPDA nanocomposite is 210nm, and this size cannot effectively remove the high permeability and retention effect (EPR effect) of solid tumors after entering the body. 2. For hydrophobic MnCO, the polydopamine loading capacity of the mesoporous structure is limited, which will directly affect the effect of cancer treatment; 3. This patent is to use the endogenous stimulation of tumors to generate Fenton reaction to generate CO to kill cancer Cells, in which the controlled release of gas is a key issue in gas therapy, it is very necessary to perform in vitro detection of gas release, but this patent does not carry out in vitro detection of gas release, and its actual therapeutic effect cannot be confirmed; 4. Tumor metastasis as At present, the primary threat to clinical cancer treatment, this patent lacks the consideration of inhibiting tumor metastasis; 5. The toxicity of the transition metal Mn used in this patent should not be underestimated in the body, and the long-term toxicity and short-term toxicity in the body should be further tracked

Method used

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  • Ammoniaborane/hollow mesoporous polydopamine/polyethylene glycol nanocomposite particles and its preparation and application
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  • Ammoniaborane/hollow mesoporous polydopamine/polyethylene glycol nanocomposite particles and its preparation and application

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Embodiment 1

[0049] Ammoniaborane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particles (AB@HMPDA-PEG) of the present invention, the nanoparticle with a composite structure uses solid silica as the core and mesoporous polydopamine as the shell, and uses The hollow mesoporous polydopamine is obtained by etching with hydrofluoric acid, and the surface of the shell is modified with PEG, and then the small-molecule prodrug of ammonia borane is encapsulated by hydrogen bond force.

[0050] (1) The preparation method of this ammonia borane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particle comprises the following steps:

[0051] (1-1) Solid silica dSiO 2 Preparation of nanoparticles: take a single-mouth bottle, add 3.15mL of ammonia water, 75mL of ethanol and 15mL of water according to the measurement of the reaction process of tetraethylorthosilicate and water, stir at 35°C for 15min, then drop in 3mL of orthosilicon Carry out hydrolysis and polymeri...

Embodiment 2

[0069] The method for preparing the ammonia borane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particles of this embodiment is basically the same as that of Example 1, except that:

[0070] In step (1-1), the addition amount of tetraethyl orthosilicate TEOS is 4 mL.

[0071] In step (1-2), dSiO dispersed in deionized water 2 The amount of nanoparticles added was 6 mL; the amount of dopamine DA added was 140 mg.

[0072] In steps (1-3), the monodisperse dSiO dispersed in deionized water 2 The addition of @PDA nanoparticles is 6mL, the addition of water is 20mL, the addition of ethanol is 20mL, and the addition of 30% hydrofluoric acid is 2mL.

[0073] In step (1-4), NH 2 - The mass concentration of mPEG in deionized water is 20mg / mL, NH 2 - The amount of mPEG added is 100 μL.

[0074] In step (1-5), the amount of ammonia borane added is 200 mg, and the amount of HMPDA-PEG composite nanoparticles is 1.5 mL.

[0075] The detection results and properties...

Embodiment 3

[0077] The method for preparing the ammonia borane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particles of this embodiment is basically the same as that of Example 1, except that:

[0078] In step (1-1), the addition amount of tetraethyl orthosilicate TEOS is 4 mL.

[0079] In step (1-2), dSiO dispersed in deionized water 2 The amount of nanoparticles added was 7 mL; the amount of dopamine DA added was 170 mg.

[0080] In steps (1-3), the monodisperse dSiO dispersed in deionized water 2 The addition amount of @PDA nanoparticles is 7mL, the addition amount of water is 20mL, the addition amount of ethanol is 20mL, and the addition amount of 30% hydrofluoric acid is 5mL.

[0081] In step (1-4), NH 2 - The mass concentration of mPEG in deionized water is 5mg / mL, NH 2 - The amount of mPEG added is 150 μL.

[0082] In step (1-5), the amount of ammonia borane added is 150 mg, and the amount of HMPDA-PEG composite nanoparticles is 1 mL.

[0083] The detecti...

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Abstract

The invention provides ammonia borane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particles, the chemical formula of the nanocomposite particles is AB@HMPDA‑PEG, with solid silica as the core and mesoporous polydopamine as the shell , etched with hydrofluoric acid to obtain hollow mesoporous polydopamine HMPDA, PEG-modified on the surface of the shell, and then encapsulated ammonia borane AB small-molecule prodrug by hydrogen bond force. The invention also provides the preparation method and application of the nanocomposite particles. Compared with the prior art, the AB@HMPDA‑PEG nanocomposite particles of the present invention can target anticancer drugs and gaseous prodrugs to the cancer site, increase the long circulation time in the body while reducing the toxic side effects on normal tissues and cells , Overcome multidrug resistance to kill cancer cells more efficiently, further improve the therapeutic effect, and have great potential in promoting the combined application of gas therapy and cancer chemotherapy, and enhancing the efficacy of cancer treatment.

Description

technical field [0001] The invention belongs to the technical field of anticancer drug carriers, and relates to an ammonia borane / hollow mesoporous polydopamine / polyethylene glycol nanocomposite particle and its preparation and application. Background technique [0002] In recent years, with the improvement of people's living standards and the aggravation of environmental pollution, cancer cases are increasing at an alarming rate, which is increasingly threatening human health. Chemotherapy, as the first-line treatment for cancer in the clinic, has seen an increase of about 70% in clinical popularity in the past 10 years, and is widely used in the treatment of cancer. However, after the systemic use of antineoplastic drugs, conventional chemotherapy will not only kill fast-growing cancer cells, but also damage normal healthy cells, resulting in serious adverse reactions, including nausea, fatigue, hair loss, diarrhea, cardiotoxicity, fertility problems, etc. Wait. On the o...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/51A61K47/34A61K47/10A61K31/704A61K33/22A61P35/00
CPCA61K9/5146A61K9/0009A61K31/704A61K33/22A61P35/00A61K2300/00
Inventor 王依婷王烨颖刘秧周靖娥杨俊飞王镜闫志强俞磊
Owner EAST CHINA NORMAL UNIV
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