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A ha-targeted double metal hydroxide-ultrasmall iron nanomaterial and its preparation and application

A technology of hydroxide and nanomaterials, applied in preparations for in vivo experiments, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc., can solve the problem of not finding doxorubicin and ultra-small iron nano Particle research reports and other issues, to achieve good blood circulation time in the body, broad prospects, and enhance the effect of nuclear magnetic resonance imaging

Active Publication Date: 2021-08-31
DONGHUA UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Searching the literature at home and abroad has not found any research reports on the preparation of layered double hydroxide-loaded doxorubicin and ultra-small iron nanoparticles and their application in tumor MR imaging / drug therapy

Method used

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  • A ha-targeted double metal hydroxide-ultrasmall iron nanomaterial and its preparation and application
  • A ha-targeted double metal hydroxide-ultrasmall iron nanomaterial and its preparation and application
  • A ha-targeted double metal hydroxide-ultrasmall iron nanomaterial and its preparation and application

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Experimental program
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Effect test

Embodiment 1

[0080] Materials Synthesis:

[0081] (1) under stirring FeCl 3 (1081mg, Adamas reagent, 500g, Batch: P1276861) was dissolved in 40mL of diethylene glycol to form a homogeneous solution. Sodium citrate (471 mg, Sinopharm, 500 g of, batch number: 20140611) was added to the solution, and the mixture was heated to 80 deg.] C in a water bath until a clear solution is formed. Subsequently, sodium acetate (1312mg, Shanghai Chemical Reagent Ling, 500 g of, batch number: 20140124) was added to the mixture and dissolved, and then the mixture was transferred to a volume of 100mL Teflon-lined stainless steel autoclave and sealed in air . The autoclave was placed in an oven at 200 ℃ 4h. After cooling to RT, the black solution was collected by centrifugation (10000rpm, 5min) and 3 times to remove excess reagents and by-product was purified with ethanol. The resulting black product was redispersed in water and lyophilized to obtain a particle size of 3.2nm Fe 3 O 4 NPs powder for further use.

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Embodiment 2

[0086] To assess LDH-Fe 3 O 4 As -HA imaging MRI contrast agents, the material to pure Fe 3 O 4 Nanoparticles r 1 Relaxivity compared, r 1 Longitudinal relaxation time relaxation rate per unit molar concentration of iron, T may be of different concentrations 1 Fitting reciprocal relaxation time is calculated. Preparation Example 1 Fe measured by ICP-AES method embodiment of the test 3 O 4 , LDH-Fe 3 O 4 And LDH-Fe 3 O 4 -HA content of Fe element. We were prepared and the Fe concentration of 1.6mM 0.1,0.2,0.4,0.8 of LDH-Fe 3 O 4 500μL -HA aqueous solution by magnetic resonance imaging analyzer material T at different concentrations of Fe 1 Relaxation effects (such as Figure 8 ). After calculated Fe 3 O 4 , LDH-Fe 3 O 4 And LDH-Fe 3 O 4 -HA of r 1 Values ​​were 0.42,5.53 and 4.38mM -1 s -1 . LDH-Fe 3 O 4 -HA of r 1 Higher than Fe 3 O 4 The r 1 value. LDH-Fe described in Example 1 was prepared 3 O 4 -HA NPs can be used as molecular MR imaging diagnosis excellent T 1 Positive contrast...

Embodiment 3

[0088] In B16 cells as a model, using the CCK-8 assay LDH-Fe 3 O 4 -HA NPs cytotoxicity and LDH-Fe 3 O 4 -HA / Antitumor effect of DOX NPs. Iron concentration of formulated 1000μg / mL LDH-Fe 3 O 4 -HA NPs mother liquor in PBS, and then formulated in the clean bench DOX concentration with sterile PBS and add 10μL of different concentrations of LDH-Fe 3 O 4-HA / PBS solution of DOX. Such that the final concentration of DOX 1.6,3.2,6.3,12.5 and 25μg / mL, the highest concentration corresponding to the content of the carrier to make a set. Overnight and sterilized with ultraviolet irradiation. The cell culture plate was placed in a 5% CO 2 , 37 ℃ continued for 24h and 48h. Then the culture was drained, washed two times with PBS, each well was then added 100μL fresh culture medium (containing 10μL CCK-8,90μL medium), cultured for 4h, the absorbance measured at 450nm using a microplate reader, and cell viability is calculated based on this value.

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Abstract

The invention relates to a HA-targeted double metal hydroxide-ultra-small iron nanomaterial and its preparation and application. Preparation: Synthesis of LDH-Fe by co-precipitation method 3 o 4 In the nanocomposite material, the activated hyaluronic acid is covalently bonded on the surface of the LDH laminate through a silane coupling agent, and finally the surface loading of anticancer drugs is carried out. The nanometer material particles of the invention are evenly distributed, and can enhance the MR imaging effect of tumor sites in animals. LDH-Fe of the present invention 3 o 4 ‑HA NPs, as the carrier of the anticancer drug doxorubicin DOX, not only has a sensitive pH-responsive release property, but also can specifically recognize tumor cells expressing CD44 receptors, thereby achieving the ideal effect of highly efficient tumor inhibition.

Description

Technical field [0001] The present invention belongs to the nano-treatment and preparation and application, and in particular, to a targeted double hydroxide HA - ultra small iron and preparation and application of nanomaterials. Background technique [0002] Construction of recent years, with the development of nanotechnology and molecular imaging, with a cancer diagnosis and treatment of functional nano-treatment platform provides the possibility of early diagnosis and individualized treatment of cancer. MR imaging because of its high sensitivity, high resolution, non-invasive advantage or radiation effect, etc., is considered one of the early clinical diagnosis of cancer the most effective. Compared with the conventional positive MR contrast agents containing Gd and Mn, ultra-small size of ferroferric oxide nanoparticles (<5nm) not only has a good T 1 Imaging, further comprising a biocompatible better, a potential high T 1 Contrast agent. However, Fe 3 O 4 Nanoparticle aggr...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/18A61K49/12A61K9/51A61K47/36A61K31/704A61P35/00
CPCA61K9/5115A61K9/5161A61K31/704A61K49/126A61K49/1863A61P35/00
Inventor 郭睿张妮史向阳
Owner DONGHUA UNIV