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A siliceous nanoparticle drug carrier and its diagnostic and therapeutic preparation and preparation method

A nanoparticle and siliceous body technology, which is applied in the field of siliceous body nano-targeted diagnosis and treatment preparations and its preparation, can solve the problem that it is difficult for organic dyes to reach the parts that need to be treated stably, the light conversion efficiency of dyes is reduced, and controlled release cannot be achieved. Effect and other issues, to achieve the effect of improving photothermal conversion efficiency and photothermal therapy and imaging effect, improving encapsulation efficiency and drug loading, and improving therapeutic effect

Active Publication Date: 2020-05-05
PEKING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the development of nano-photothermal materials, organic dyes have attracted widespread attention for their extremely low biological toxicity and good photothermal conversion efficiency. At present, more research hotspots are also on organic dyes. However, organic dyes are in the near-infrared Photobleaching is prone to occur after multiple times of light irradiation, and the photoconversion efficiency of the dye is significantly reduced, which is not conducive to reuse, and it is difficult for a single organic dye substance to enter the body to reach the site that needs to be treated stably. Therefore, it is constructed by assembling into nanoparticles. The nano-platform system integrates photothermal therapy and diagnosis and treatment. These photothermal nano-therapeutic agents have good photothermal conversion efficiency, and can realize multifunctional applications through surface modification or bonding with other materials, which have been demonstrated in animal experiments. Excellent curative effect, worthy of people to continue to explore, has great prospects
[0004] For the treatment of tumors, simple photothermal therapy is likely to lead to recurrence, and it is difficult to inhibit tumor metastasis, while simple chemotherapy cannot achieve a controlled release effect, and has high toxicity to non-tumor tissues and organs

Method used

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  • A siliceous nanoparticle drug carrier and its diagnostic and therapeutic preparation and preparation method
  • A siliceous nanoparticle drug carrier and its diagnostic and therapeutic preparation and preparation method
  • A siliceous nanoparticle drug carrier and its diagnostic and therapeutic preparation and preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] A preparation scheme of the preparation described in the present invention is as attached figure 1 shown, including the following steps:

[0061] 1) Synthesis of methine dyes: indoline structure 2 prepared by Fischer addition of structure 1 and ketones, structure 3 and structure 4 were obtained by substitution reaction, structure 3 and methine conjugated chain containing resonance structure Small molecule-like structure 5 was dispersed in acetic anhydride under nitrogen protection and stirred at 120°C to obtain structure 6. Structure 6 and the indoline structure monomer at the other end were dispersed in triethylamine for substitution reaction to form structure 7, namely methine Cyanine fluorescent dye 7, the structure of each compound is as follows Figure 8 shown;

[0062] The specific operation is as follows:

[0063] Add 0.57g of phenylhydrazine, 1.68ml of 3-methyl-2-butanone and 3ml of glacial acetic acid into a 50ml round bottom flask, heat and stir for 3h to o...

Embodiment 2

[0077] The small animal near-infrared fluorescence imaging effect evaluation of the preparation prepared in Example 1 mainly includes the following steps:

[0078] (1) Establishment of subcutaneous tumor model in nude mice: HT-29 cells were injected into each nude mouse at 2×10 6 The amount of cells was inoculated subcutaneously on the outer thigh of BALB / c nude mice, and the nude mice were raised under SPF environment;

[0079] (2) The size of the tumor grows to about 100mm 3 100 μL of 4 mg / mL of the preparation prepared in Example 1 was injected through the tail vein, and at different times after administration, the fluorescence intensity signal of the tumor site was detected with a small animal near-infrared fluorescence imaging system.

[0080] The imaging results are attached Figure 4 As shown, after injecting the preparation, the near-infrared signal of the tumor site gradually increased, and reached the strongest near-infrared fluorescence signal at 8 hours, and diff...

Embodiment 3

[0082] (1) Investigation of photothermal heating stability: Add 3ml of siliceous nanoparticle with equal concentration, fluorescent dye and undoped composite liposome solution into quartz cuvette, and use 808±10nm wavelength and 2W / cm 2 The output power of the solution is irradiated with a near-infrared laser of a continuous wave diode, and the temperature of the solution is measured every 10 seconds with a digital thermometer and a thermocouple probe for a total of 10 minutes, then cooled to room temperature, and repeated three times. Record the temperature rise after 10 minutes of irradiation. This experiment required three parallel experiments.

[0083] (2) Investigation of structural stability: non-ionic surfactant Triton X-100 with different volume ratios was added to different nanoparticles dissolved in PBS and serum, incubated at 37°C, and then treated with Malvern Zetasizer Nano-ZS90 Determine the particle size of the nanoparticles. This experiment also required thre...

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Abstract

The invention discloses a siliceous nanoparticle drug carrier, a diagnostic therapeutic preparation thereof and a preparation method. The carrier is a vesicle having a lipid bilayer structure formed by doping hydration and self-assembly of a fluorescent amphiphilic molecule and a silicon-containing composite liposome, wherein the fluorescent amphiphilic molecule is a compound taking a glycerol skeleton structure as a core and formed by a bonded hydrophobic long chain and a fluorescent group; the silicon-containing composite liposome is composed of a silicon-containing inorganic precursor, a hydrophobic lipid chain, and a linking group coupling the silicon-containing inorganic precursor and the hydrophobic lipid chain, and the silicon-containing inorganic precursor of the silicon-containingcomposite liposome is hydrolyzed and then hydrolysis products are condensed to form an inorganic silicate network structure distributed on the surface of the vesicle. The diagnostic and therapeutic preparation prepared by using the carrier to load a drug has high stability, combines two drug controlled release mechanisms, that is pH and photothermal response, and enhances the stability of the fluorescent group. Through combination of chemotherapy and photothermal therapy, the recurrence rate of tumors is effectively reduced.

Description

technical field [0001] The invention belongs to the field of biomedical materials, and specifically relates to a siliceous body nanoparticle drug carrier, a siliceous body nano-targeted diagnosis and treatment preparation with high stability and drug controlled release function, and a preparation method thereof. Background technique [0002] The use of nanoparticle platforms for diagnosis and treatment is one of the important means of cancer treatment. Among them, liposomes are widely used. Liposome means that when phospholipids are dispersed in water, multilayered vesicles can be formed by electron microscope observation, and each layer is a lipid bilayer, and the center of the vesicle and each layer are separated by water to form a closed vesicle Bubble. It can be composed of natural or synthetic lipids. These molecules are composed of a hydrophilic head and a lipophilic tail. The thickness of the membrane wall is generally 5-7nm. Since the chemical components of cell m...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K49/00A61K9/127A61K47/04A61K31/704A61P35/00
CPCA61K9/1271A61K31/704A61K41/0052A61K47/02A61K49/005A61K49/0084A61P35/00A61K2300/00
Inventor 王凡梁晓龙张旭李小达史继云马晓途侯睿
Owner PEKING UNIV
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