A gold nano-drug carrier with dual effects of overcoming and avoiding p-glycoprotein-mediated tumor multidrug resistance

A multi-drug resistance and P-glycoprotein technology, applied in the direction of anti-tumor drugs, medical preparations with non-active ingredients, medical preparations containing active ingredients, etc.

Active Publication Date: 2015-10-28
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Through literature search, no patents or literature reports on the use of multifunctional gold nanomaterials as paclitaxel carriers to combat Pgp-mediated multidrug resistance and avoid such drug resistance have been found.

Method used

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  • A gold nano-drug carrier with dual effects of overcoming and avoiding p-glycoprotein-mediated tumor multidrug resistance
  • A gold nano-drug carrier with dual effects of overcoming and avoiding p-glycoprotein-mediated tumor multidrug resistance
  • A gold nano-drug carrier with dual effects of overcoming and avoiding p-glycoprotein-mediated tumor multidrug resistance

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Preparation of 15nm gold nanomaterials:

[0063] 104.56 mg (0.25 mmol) HAuCl 4 4H 2 0 dissolved in 300mL PALL water, heated to boiling. Dissolve 264mg (0.90mmol) of sodium citrate in 30mL of PALL water, preheat to 80°C and quickly add to the above boiling solution. The color of the solution quickly changed to blue-purple and finally wine red. In boiling state, continue to stir for 10 min, then cool to room temperature naturally. by and (0.22μm, Millipore) filter, adjust the pH to 8.0 with 0.5M NaOH solution, measure the gold element content by inductively coupled plasma mass spectrometry (ICP-MS) and adjust the concentration of nanomaterials to 5nM, set aside.

Embodiment 2

[0065] Preparation of drug-loaded ligand (CD-SH):

[0066]

[0067] Preparation of β-cyclotine sulfonate (CD-OTs): In an ice bath, 3.0 g (1.6 mmol) of β-cyclotine was dispersed in 25 mL PALL water, and 8.2 M NaOH solution was added dropwise under stirring, followed by With the addition of NaOH, cyclodextrin gradually dissolved in water. Afterwards, 1 mL of acetonitrile solution containing 437 mg (2.3 mmol) p-toluenesulfonyl chloride was added dropwise, and a white precipitate was formed immediately. After stirring for 4 hours at room temperature, the pH of the reaction system was adjusted to 6 with 3M hydrochloric acid. The white precipitate was obtained by filtration, and recrystallized twice to finally obtain β-cycloquine sulfonate (CD-OTs, 1.1 g, yield 53.3%). HR-MS (m / z): 1289.3796 (MH + ).

[0068] Preparation of amino β-cyclotine (CD-EDA): Dissolve 1.0g of β-cyclotine sulfonate (CD-OTs, 0.8mmol) in 4mL of ethylenediamine, stir at 70°C for 4h under nitrogen protecti...

Embodiment 3

[0071] Preparation of novel gold nano drug carrier:

[0072] synergistic ligand NH 2 -PEG5000-SH6mg (1.2mmol) was added to 200mL of 15nm gold nano stock solution under stirring, and stirred vigorously at 4°C for 24h. With stirring, 50 μL of the PBS solution of the drug-loaded ligand CD-SH was added to the above solution, and the stirring was continued at 4° C. for 24 h. The reaction mixture was placed in a 10KD centrifugal filter, and centrifuged at 5000g for 30 minutes to separate and remove excess ligand; the separated solid was dissolved in deionized water, and after conventional ultrasonic treatment, centrifuged again at 5000g for 30± 5 minutes, and repeated centrifugation and washing 6 times (PALL water, 40mL×6). After the last washing step, the gold nanocarriers were dissolved in 5mL high-purity water and used as the original solution. After digestion, the gold element was determined by ICP-MS method content, and adjust the concentration of gold nano drug carrier to 100n...

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Abstract

The invention discloses a gold medicinal nano-carrier with double functions of overcoming and preventing P-glycoprotein-mediated tumor multidrug resistance. The gold medicinal nano-carrier is prepared by connecting a synergistic hydrophilic ligand for enhancing intake of nano-materials and a medicine-carrying ligand for carrying hydrophobic medicines to a gold nano-material by a ligand exchange method, wherein the synergistic hydrophilic ligand is a thiolated PEG 5000 (polyethylene glycol 5000) molecule with electropositive amino group at the terminal, and the medicine-loading ligand is a thiolation modified beta-cyclodextrin molecule; the gold medicinal nano-carrier is of a spherical shape. Experiments prove that a paclitaxel-loaded gold medicinal nano-carrier prepared by adsorbing the gold nano-carrier to paclitaxel can be used for effectively killing cells with P-glycoprotein drug resistance, can avoid drug resistance generation while killing cells without P-glycoprotein drug resistance, and provides a new thought and new direction to nano-medicine loading methods in overcoming tumor multidrug resistance.

Description

technical field [0001] The present invention relates to a drug carrier based on gold nanomaterials, in particular to a drug carrier capable of combating P-glycoprotein-mediated tumor multidrug resistance while avoiding P-glycoprotein (Pgp)-mediated multidrug resistance. Gold nano-drug carriers for drug resistance. Background technique [0002] In addition to surgical resection and radiotherapy, chemotherapy is currently the most important means of cancer treatment. However, the generation of tumor multidrugs eventually leads to the failure of most chemotherapeutic drugs (Lage2008), and even the latest molecularly targeted small molecule drugs cannot avoid this problem. It is generally believed that the ABC transporter family on the cancer cell membrane, especially the drug efflux mediated by P-glycoprotein, leads to the multidrug resistance of tumors (Sakaeda, Nakamura et al.2003; Paterson et al. 2006). Therefore, there is an urgent need for a drug that can specifically ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/34A61K47/48A61K47/40A61K47/02A61K31/337A61P35/00
Inventor 闫兵李飞翟淑梅张斌
Owner SHANDONG UNIV
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