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Polyamino acid coordination nanoparticles, preparation method thereof and application thereof serving as drug for acoustodynamic oncotherapy

A polyamino acid and nanoparticle technology, which is applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulations, can solve the problems of poor biological safety and water insolubility, and achieve uniform particle size, good dispersibility, and good sound-sensitizer properties. Effect

Active Publication Date: 2019-09-06
BEIJING UNIV OF CHEM TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, coordination nanoparticles such as MOF-5 and ZIF-8, which are widely used in the fields of photocatalysis and biological applications, mostly face the problems of poor biological safety and water insolubility.

Method used

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  • Polyamino acid coordination nanoparticles, preparation method thereof and application thereof serving as drug for acoustodynamic oncotherapy
  • Polyamino acid coordination nanoparticles, preparation method thereof and application thereof serving as drug for acoustodynamic oncotherapy
  • Polyamino acid coordination nanoparticles, preparation method thereof and application thereof serving as drug for acoustodynamic oncotherapy

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Experimental program
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Effect test

Embodiment 1

[0032] (1) 0.1mmol of γ-PGA dissolved in 50mM, 2mL NaHCO 3 The solution was placed in a 10mL reaction bottle, and stirred at room temperature until completely dissolved.

[0033] (2) Put the reaction bottle into a 100mL beaker and add appropriate amount of ice cubes for ice bath. First add 0.1mmol N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) to the reaction flask, then add 0.1mmol N-hydroxysuccinimide (NHS), ice React under bath conditions for 10 minutes.

[0034] (3) Add 0.1 mmol phenylalanine ethyl ester (F) and 0.2 mmol histidine methyl ester (H) successively to the reaction flask, and react for 1 h under ice bath conditions; remove the ice bath after 1 h, and react at room temperature 12h.

[0035] (4) Transfer all the 2mL samples in the reaction bottle to the dialysis bag, clamp both ends with clips, put it into a beaker for dialysis, change the water every 3 hours, and continue dialysis for 2 days.

[0036] (5) Transfer the sample from the dialys...

Embodiment 2

[0039] (1)-(5) is the same as embodiment 1 step (1)-(5)

[0040] (6) Dissolve PFH in 100 μL of dimethylsulfoxide (DMSO) to prepare a 5 mg / mL solution.

[0041] (7) FeSO 4 ·7H 2 O was dissolved in 900 μL DMSO to make 8 mM FeSO 4 solution.

[0042] (8) Add the PFH solution obtained in (6) into (7), and stir for 24 hours at room temperature. Then centrifuged at 14,000 rpm for 5 min and washed three times with water to obtain polyamino acid coordination nanoparticles γ-PGA-g-F-H / Fe 2+ / Fe 3+ (PFHF).

[0043] The obtained PFHF nanospheres, using the fitting parameter table and fitting curve obtained by Extended X-ray Absorption Fine Structure (Extended X-ray Absorption Fine Structure, EXAFS), show that the coordination number of the PFHF coordination nanoparticles is 5.9, and the coordination number is 5.9. Bit key length is

Embodiment 3

[0045] (1)-(5) are the same as embodiment 1 steps (1)-(5).

[0046] (6) Dissolve PFH in 100 μL dimethylsulfoxide (DMSO) to prepare a 5 mg / mL solution; dissolve 1 mg doxorubicin hydrochloride (DOX·HCl) in 100 μL DMSO, add 2.5 μL triethylamine, Stir overnight.

[0047] (7) FeSO 4 ·7H 2 O was dissolved in 900 μL DMSO to make 8 mM FeSO 4 solution.

[0048] (8) Add the PFH solution and DOX solution (25 μL, 10 mg / mL) in (6) to (7) sequentially, and react for 24 hours at room temperature. Then 14000rpm, 5min centrifugal washing three times to get γ-PGA-g-F-H / Fe 2+ / Fe 3+ / DOX(PFHDF)

[0049] The particle diameter of the obtained PFHDF nano microsphere is about 160nm.

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Abstract

The invention discloses polyamino acid coordination nanoparticles, a preparation method thereof and application thereof serving as drug for acoustodynamic oncotherapy. The preparation method includes:grafting two micromolecular amino acids, phenylalanine ethyl ester, F and histidine methyl ester, H on gamma-polyglutamic acid (gamma-PGA) side chain to synthesize gamma-PGA-g-F-H (PFH); taking PFH as a ligand to be in coordination reaction with Fe2+ / Fe3+ while wrapping hydrophobic doxorubicin (DOX) to form nanoparticles (PFH / Fe2+ / Fe3+ / DOX, PFHDF) of about 160nm in particle size. The method is simple in operation, short in consumed time, low in synthesis cost and mild in synthesis condition. The nanoparticles are high biocompatibility, can present characteristics of acousto-sensitive agents,generate a lot of active oxygen and release DOX under ultrasonic effect and have remarkable acoustodynamic-chemotherapy synergistic treatment effect, and anti-tumor rate reaches 85%.

Description

technical field [0001] The invention belongs to the field of nanometer material and its preparation, and in particular relates to a polyamino coordination nanoparticle with sound sensitizer properties, a preparation method thereof and a medicine in the direction of sonodynamic tumor treatment. Background technique [0002] Based on the different redox states between normal cells and cancer cells, it has been recognized that excessive generation of reactive oxygen species near tumors can induce cancer cell death. Photodynamic therapy, which mainly generates reactive oxygen species through light-induced photosensitizers to kill tumor cells, has been widely used as a non-invasive therapy. However, its further clinical application is limited due to the weak penetration of light into tissues. Ultrasound triggers the sonosensitizer to generate active oxygen, that is, sonodynamic therapy. As a new non-invasive cancer treatment, it has obvious advantages compared with photodynamic ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/34A61K41/00A61K31/704A61P35/00
CPCA61K9/5146A61K31/704A61K41/0033A61P35/00A61K2300/00
Inventor 申鹤云王明坤刘惠玉
Owner BEIJING UNIV OF CHEM TECH
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