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HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof

A hydroxide and nanomaterial technology, which is applied to preparations for in vivo testing, medical preparations without active ingredients, and medical preparations containing active ingredients, etc., can solve the problem of not finding doxorubicin and ultra-small iron nanoparticles. Particle research reports, etc.

Active Publication Date: 2019-07-16
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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  • HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof
  • HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof
  • HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof

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Embodiment 1

[0080] Synthesis of materials:

[0081] (1) Mix FeCl under stirring 3 (1081 mg, Adamas reagent, 500 g, batch: P1276861) was dissolved in 40 mL of diethylene glycol to form a homogeneous solution. Sodium citrate (471 mg, Sinopharm Group, 500 g, batch number: 20140611) was added to the above solution, and the mixture was heated to 80° C. in a water bath until a clear solution was formed. Subsequently, sodium acetate (1312 mg, Shanghai Lingfeng Chemical Reagent, 500 g, batch number: 20140124) was added to the above mixture solution and dissolved, and then the mixture was transferred to a Teflon-lined stainless steel autoclave with a volume of 100 mL and sealed in air . The autoclave was placed in an oven at 200 °C for 4 h. After cooling to room temperature, the black solution was collected by centrifugation (10000 rpm, 5 min) and purified 3 times with ethanol to remove excess reactants and by-products. The resulting black product was redispersed into water and lyophilized to ...

Embodiment 2

[0086] To evaluate LDH-Fe 3 o 4 - Imaging effect of HA as an MRI contrast agent, combining the material with pure Fe 3 o 4 r of nanoparticles 1 Relaxation rate for comparison, r 1 The relaxation rate is the longitudinal relaxation time per molar concentration of iron, which can be changed by different concentrations of T 1 The inverse of the relaxation time was calculated by fitting. Measure the Fe prepared in Example 1 by ICP-AES test method 3 o 4 , LDH-Fe 3 o 4 and LDH-Fe 3 o 4 - Content of Fe element in HA. Prepare LDH-Fe with Fe concentration of 0.1, 0.2, 0.4, 0.8 and 1.6mM respectively 3 o 4 -500 μL of HA aqueous solution, the T of the material at different Fe concentrations was measured by a magnetic resonance imaging analyzer 1 relaxation effects (such as Figure 8 ). Calculated Fe 3 o 4 , LDH-Fe 3 o 4 and LDH-Fe 3 o 4 -HA r 1 The values ​​are 0.42, 5.53 and 4.38mM respectively -1 the s -1 . LDH-Fe 3 o 4 -HA r 1 higher than Fe 3 o 4 the r ...

Embodiment 3

[0088] Using B16 cells as a model, using CCK-8 method to detect LDH-Fe 3 o 4 - Cytotoxicity of HA NPs and LDH-Fe 3 o 4 -In vitro anticancer effect of HA / DOX NPs. The concentration of prepared iron is 1000μg / mL LDH-Fe 3 o 4 -The PBS mother solution of HA NPs, and then prepare the concentration of DOX with sterile PBS on the ultra-clean bench and add 10 μL of LDH-Fe of different concentrations 3 o 4- HA / DOX in PBS. The final DOX concentration was 1.6, 3.2, 6.3, 12.5 and 25 μg / mL, and the carrier content corresponding to the highest concentration was used as a group. And sterilized overnight with ultraviolet radiation. Place the cell culture plate in 5% CO 2 , continue to incubate at 37°C for 24h and 48h. Then discard the culture medium, wash it twice with PBS, add 100 μL new culture medium (containing 10 μL CCK-8, 90 μL culture medium) to each well, continue to cultivate for 4 h, measure the absorbance at 450 nm with a microplate reader, and Based on this value, the v...

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Abstract

The invention relates to a HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof. The preparation is as follows: synthesizing an LDH-Fe3O4 nano composite material by a coprecipitation method; covalently bonding activated hyaluronic acid on the surface of an LDH laminate through a silane coupling agent; and finally, carrying out surface loadingof an anticancer drug. The nano-material particles are uniformly distributed, and can enhance the MR imaging effect of the tumor part in an animal body. The LDH-Fe3O4-HA NPs is used as a carrier of ananticancer drug doxorubicin DOX, not only has sensitive pH response and release characteristics, but also can carry out specific recognition on tumor cells expressed by CD44 receptors so as to achieve the idealization effect of efficiently inhibiting tumors.

Description

technical field [0001] The invention belongs to the field of nano-diagnosis and treatment agent and its preparation and application, in particular to an HA-targeted double metal hydroxide-ultrasmall iron nanometer material and its preparation and application. Background technique [0002] In recent years, with the development of nanotechnology and molecular imaging, the construction of a nanodiagnosis and treatment platform with tumor diagnosis and treatment functions provides the possibility for early diagnosis and individualized treatment of tumors. MR imaging is regarded as one of the most effective clinical diagnostic techniques for early cancer due to its advantages of high sensitivity, high resolution, and no trauma or radiation effects. Compared with the commonly used MR positive contrast agents containing Gd and Mn, the ultra-small size of ferric oxide nanoparticles (<5nm) not only has good T 1 Imaging effect, also has better biocompatibility, is a potential high...

Claims

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Application Information

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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
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