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Preparation and application of drug-loaded polydopamine/dendrimer-gold nanoparticles

A polydopamine nano- and dendrimer technology, which can be used in medical preparations with non-active ingredients, medical preparations containing active ingredients, photosplitting of drugs in vivo, etc., and can solve problems such as insufficient exploration. , to achieve good biocompatibility, significant tumor growth, and broad application prospects.

Active Publication Date: 2021-09-24
SOUTHWEST UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Based on this, the construction of a nano-scale "vehicle" that incorporates all the above-mentioned functions has great potential, but has not been fully explored

Method used

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  • Preparation and application of drug-loaded polydopamine/dendrimer-gold nanoparticles
  • Preparation and application of drug-loaded polydopamine/dendrimer-gold nanoparticles
  • Preparation and application of drug-loaded polydopamine/dendrimer-gold nanoparticles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Take 2.6 mL, 90 mL, and 40 mL of ammonia water, ethanol, and distilled water respectively, and magnetically stir them in a 45°C water bath to fully mix them. After 15 minutes, 10 mL of 50 mg / mL dopamine monomer aqueous solution was added. After reacting for 12 h, the polydopamine nanoparticles were collected by centrifugal purification (16000 rpm, 10 min).

[0046] According to the molar ratio of 1:50, the dendrimer and the chloroauric acid aqueous solution were mixed, stirred and mixed at room temperature for 15 minutes. Then, according to the molar ratio of 1:3, sodium borohydride aqueous solution was added, and the reaction was stirred for 2 hours. After the reaction, the solution was dialyzed for 2 days (6 times, 1 L / time), and freeze-dried to obtain the dendrimer-gold nanoparticles.

[0047] According to the mass ratio of 1:0.5, the polydopamine nanoparticles were slowly added dropwise into the dendrimer-gold nanoparticles, and the reaction solution was 10 mM Tri...

Embodiment 2

[0051] Prepare an ethanol solution of doxorubicin hydrochloride, and add it to the aqueous solution of PDA-G5Au-PEG nanoparticles prepared in Example 1 at a mass ratio of 1:1. After stirring and mixing, triethylamine was added. After 24 hours of reaction, the drug-loaded polydopamine / dendrimer-gold (PDA-G5Au-PEG@DOX) composite nanoparticles were obtained by centrifugation and water washing purification.

[0052] UV-Vis spectrum display (attached figure 2 a), There is an obvious absorption peak around 480 nm, indicating the successful loading of doxorubicin. Field emission electron microscope photos show (attached figure 2 b) shows that the morphology of PDA-G5Au-PEG@DOX nanoparticles is relatively uniform. The test results of laser particle size analyzer (DLS) showed the hydrodynamic size and uniformity of the obtained composite nanoparticles. Refer to the attached figure 2 c. The average size of PDA-G5Au-PEG@DOX composite nanoparticles is 219.4 ± 0.2 nm.

Embodiment 3

[0054] Take the PDA-G5Au nanoparticles prepared in Example 1, put them in the buffer solution of pH 7.4 and pH 6.4, place them on a constant temperature shaker at 37°C, and take samples after 0, 6, 12, and 24 hours respectively, and collect the products. PDA-G5Au-PEG@DOX nanoparticles were placed under different conditions (pH7.4 buffer, pH6.4 buffer, 20 mM hydrogen peroxide, 1.75 W / cm 2 laser irradiation), placed in a constant temperature shaker, and samples were taken regularly to study the release of the chemotherapy drug DOX.

[0055] Transmission electron microscope photos show (attached image 3 a), After shaking for 24 hours, the small black particles on the PDA "core" at pH 6.4 were significantly less than those at pH 7.4. This suggests that mildly acidic conditions can promote the release of "satellite" G5Au nanoparticles. Inductively coupled plasma optical emission spectroscopy (ICP-OES) test analysis (attached image 3 b) It was found that under the condition of ...

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Abstract

The present invention relates to the preparation and application of a drug-loaded polydopamine / dendrimer-gold nanoparticle, comprising: modifying the dendrimer-gold nanoparticle to the surface of the polydopamine nanoparticle, and performing polyethylene glycol modification and Anticancer drug doxorubicin loading. The resulting “core-satellite”-structured composite nanoparticles can acid-responsively release small-sized “satellites” to achieve deep tumor drug delivery and alleviate drug resistance caused by tumor hypoxia; both internally (acid and hydrogen peroxide) and externally ( Near-infrared light) stimulates the release of doxorubicin at a fixed point. The obtained composite nanoparticles have good biocompatibility, can realize photoacoustic diagnosis and photothermal therapy on tumor sites, and more importantly, can realize significant inhibitory effect on tumor growth. The method of the invention can significantly improve the therapeutic effect of traditional chemical drugs, realize more comprehensive and three-dimensional tumor treatment, and provide a new idea for the diagnosis and treatment of malignant tumors.

Description

technical field [0001] The invention belongs to the field of preparation of nano-diagnosis and treatment agents for hypoxic tumors, in particular to a preparation method of drug-loaded polydopamine / dendrimer-gold composite nanoparticles with a "nuclear-satellite" structure and its application in hypoxic tumors. Integrated application of diagnosis and treatment in photoacoustic imaging / photothermal therapy / chemotherapy. Background technique [0002] Chemotherapy, as a routine clinical tumor treatment, has been widely used. However, in order to fully exert its drug efficacy, chemical drugs must reach the tumor site. However, due to their unique properties, such as fast blood pool metabolism and poor water solubility, most anticancer drugs are often difficult to achieve good therapeutic effects. In order to improve the therapeutic effect of cancer, studies have shown that designing and building nano "vehicles" to load chemical drugs can significantly improve the effect of che...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/22A61K41/00A61K9/51A61K47/34A61K47/10A61K31/704A61P35/00
CPCA61K9/5146A61K31/704A61K41/0042A61K41/0052A61K49/225A61P35/00A61K2300/00
Inventor 刘辉王静静谷达冲阳文婷胡洁唐薇
Owner SOUTHWEST UNIV
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