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Up-conversion nanoparticles and application thereof in light-operated induction of MSC cartilage differentiation and tracing imaging

A nanoparticle and nanocomposite technology, which is applied in nano-optics, photo-splitting of drugs in vivo, medical preparations of inactive ingredients, etc., can solve problems such as reducing efficiency, achieve high yield and improve drug delivery efficiency. , good stability

Pending Publication Date: 2021-09-28
SOUTH CHINA NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the poor water solubility of KGN reduces its efficiency in cells. How to improve its cell targeting and bioavailability and reduce its cytotoxicity is the key to KGN's clinical treatment of osteoarthritis.

Method used

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  • Up-conversion nanoparticles and application thereof in light-operated induction of MSC cartilage differentiation and tracing imaging
  • Up-conversion nanoparticles and application thereof in light-operated induction of MSC cartilage differentiation and tracing imaging
  • Up-conversion nanoparticles and application thereof in light-operated induction of MSC cartilage differentiation and tracing imaging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] A preparation method for upconversion nanoparticles, comprising the following steps:

[0039] 1) YCl 3 ·6H 2 O (482.3mg, 1.59mmol), YbCl 3 ·6H 2O (155.0mg, 0.4mmol), TmCl 3 ·6H 2 O (2.75mg, 0.01mmol), ErCl 3 ·6H 2 O (1.91mg, 0.005mmol) was dissolved in 10mL of methanol, and after fully dissolved, 15mL of oleic acid and 30mL of octadecene were added, and the temperature was raised to 110°C. After the above mixed solution became a light yellow transparent solution, the temperature was lowered to room temperature, and then NaOH was added. -Methanol solution (NaOH 296.3mg, 8mmol) and NH 4 F-methanol solution (NH 4 F 200mg, 5mmol), stirred and emulsified at room temperature for 0.5h. After the emulsification was completed, the temperature of the above mixed solution was slowly raised to 120° C., methanol in the system was removed, and then the temperature was slowly raised to 310° C. and kept for 1 h. After the heating was completed, the solution was cooled, and th...

Embodiment 2

[0046] The nanocomposite of loading KGN is prepared by the following steps:

[0047] 10mg UCNP@mSiO 2 -azo-RGD was dispersed into 10mL KGN-ethanol solution with a concentration of 0.025mg / mL, and stirred at room temperature for 24h. The drug small molecule KGN was loaded into the mesoporous pores by physical adsorption, and the product was collected by centrifugation to obtain the KGN-loaded nanocomposite (UCNP@mSiO 2 -azo-RGD / KGN, UCNP / KGN).

[0048] Investigate the release rate of KGN in the nanocomposites loaded with KGN obtained under different power near-infrared light irradiation, the results are as follows image 3 shown. at 1.5W / cm 2 Under near-infrared light irradiation, the KGN release rate reached 33wt% within 165 minutes, at 2.0W / cm 2 Under irradiation, the release rate of KGN reached a maximum of 45wt%, which indicated that the drug release rate was enhanced with the increase of light time and light intensity time. Power is 0W / cm 2 (without near-infrared li...

Embodiment 3

[0051] A method for inducing MSC chondrogenic differentiation in vitro, comprising the following steps:

[0052] 1) MSCs were inoculated into a six-well plate, and after culturing for 24 hours, they were divided into five groups, namely Group A (blank control Control), Group B (with KGN added), and Group C (with the nanocomposite UCNP added in Example 1), Group D (adding the nanocomposite UCNP / KGN loaded with KGN in Example 2), group E (adding the nanocomposite UCNP / KGN+NIR loaded with KGN in Example 2). The concentration of KGN in group B was 100nM, and the concentration of nanocomposites in groups C, D, and E was 0.2mg / mL. Incubate together for 2 to 5 hours. After the incubation, wash the cells with PBS. Group E’s near-infrared light irradiation lasts for 30 minutes, that is, illuminates for 5 minutes, stops for 5 minutes, and then illuminates for 5 minutes. The total irradiation time is 30 minutes, and the irradiation power is 1.5W / cm 2 , the whole process is only irradiat...

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Abstract

The invention discloses up-conversion nanoparticles and application thereof in light-operated induction of MSC (mesenchymal stem cell) cartilage differentiation and tracing imaging. According to the up-conversion nanoparticles, the surface of a mesoporous silicon layer is modified with cell-targeted polypeptide RGD. KGN and the up-conversion nanoparticles are stirred for reaction and centrifuged to obtain the KGN-loaded nano-composite. The nano-composite loaded with the KGN and MSC are co-incubated, and then the cells are irradiated by using near-infrared light to promote the nano-composite loaded with the KGN to release small drug molecules KGN to induce the MSC to be directionally differentiated into cartilage cells; and the differentiated MSC is traced and imaged through 545 / 647 nm fluorescence emitted by the up-conversion nanoparticles. The nano-composite disclosed by the invention has a cell targeting effect, and the drug KGN can be released only when 980nm near-infrared illumination exists outside, so that cartilage differentiation of stem cells is induced; and the cell imaging can be traced for a long time, and the positioning is provided for the MSC in the transplantation body.

Description

technical field [0001] The invention relates to an up-converting nanoparticle and its application in light-controlled induction of MSC cartilage differentiation and tracer imaging. Background technique [0002] Bone marrow mesenchymal stem cells (MSCs) are stem cells derived from bone marrow that can be differentiated under the induction of specific inducing factors, and have high proliferation ability and multilineage differentiation potential. Studies have found that MSC can be directional differentiated into chondrocytes, osteoblasts, fat cells, nerve cells and other tissue cells. [0003] Because MSCs have multiple differentiation potentials and are easy to collect, they have become a type of cell widely used in regenerative medicine and tissue engineering. Among them, specifically inducing MSCs to differentiate into chondrocytes provides the possibility for clinical treatment of diseases such as osteoarthritis, and has huge market value and research significance. How ...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/64A61K41/00A61K31/196A61K49/00G01N21/64C12N5/077A61P19/02A61P19/08A61P29/00B82Y5/00B82Y20/00B82Y30/00B82Y40/00
CPCA61K47/6923A61K41/0057A61K47/64A61K31/196A61K49/0017A61K49/0093A61K41/0042A61P19/02A61P19/08A61P29/00B82Y5/00B82Y20/00B82Y30/00B82Y40/00C12N5/0655G01N21/6486C12N2501/999C12N2506/1353C12N2529/10
Inventor 黎锦明杨子涵郭玉娇闫瑞
Owner SOUTH CHINA NORMAL UNIVERSITY
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