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Nitric oxide and cisplatin targeted combined controllable delivery nano drug system and its preparation

A nano-carrier and drug technology, applied in the field of multifunctional bimetallic nano-composite drug system and its preparation, to achieve good biocompatibility, stability, and high-efficiency anti-cancer effects

Active Publication Date: 2022-02-08
EAST CHINA UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Based on the above analysis, how to selectively deliver the extremely unstable small molecule of NO to specific cells or subcellular organelles at an appropriate concentration, combine NO with other chemotherapy drugs, and improve the anticancer effect of the drug through controllable combined administration Efficacy is yet to be studied

Method used

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  • Nitric oxide and cisplatin targeted combined controllable delivery nano drug system and its preparation
  • Nitric oxide and cisplatin targeted combined controllable delivery nano drug system and its preparation
  • Nitric oxide and cisplatin targeted combined controllable delivery nano drug system and its preparation

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preparation example Construction

[0141] The present invention also provides a preparation method of the pharmaceutical system of the present invention, which generally includes the following steps:

[0142] (1) Provide metal nitrosyl NO donors, platinum complexes, targeting groups and carrier nanoparticles;

[0143] (2) covalently loading the metal nitrosyl NO donor, the platinum complex, the targeting group and the carrier nanoparticles to form the bimetallic nanocomposite drug system .

[0144] In another preferred example, in step (1), the metal nitrosyl NO donor includes a metal nitrosyl compound (A)[(tpy')M 1 (R 1 )(NO)](PF 6 ) 3 , tpy' is 4'-formic acid-2,2':6',2"-terpyridine, M 1 For metal ruthenium (Ru), R 1 For 3-formic acid-o-phenylenediamine or its derivatives.

[0145] In another preferred example, in step (1), the platinum complex includes metal compound (B) cis-[M 2 (NH 3 ) 2 Cl 2 (OH) 2 ], M 2 For the metal platinum (Pt).

[0146] In another preferred example, the carrier nanopart...

Embodiment 1

[0159] Metal Ru nitrosyl compounds [(tpy COOH )Ru(MDAB)(NO)](PF 6 ) 3 Synthesis

[0160] (1)[(tpy COOH )Ru(MDAB)(Cl)](PF 6 )Synthesis

[0161] (tpy COOH is 4'-formic acid-2,2':6',2"-terpyridine; MDAB is methyl 3,4-diaminobenzoate):

[0162] Add Ru(tpy COOH ) Cl 3 (150mg, 0.31mmol), MDAB, (55mg, 0.33mmol), LiCl (5mg, 2.0mmol) and Et 3 N 0.4mL, vacuumize and nitrogen three times respectively, add 40mL of EtOH / H 2 O(3:1, v / v), in N 2 Reflux in the atmosphere for 8 hours, suction filter while hot, and concentrate the dark red filtrate to several milliliters. After cooling to room temperature, add excess saturated NH 4 PF 6 solution, and the mixture was placed in a refrigerator at 5°C overnight. The reddish-brown precipitate was filtered out and washed with H 2 O and Et 2 O were washed three times, respectively, and dried in vacuo. 137 mg of the target product was obtained with a yield of 61%.

[0163] (2)[(tpy COOH )Ru(MDAB)(NO 2 )](PF 6 )Synthesis:

[0164] W...

Embodiment 2

[0169] Synthesis of Nanoparticle Composite Drug System {N-GQDs@Ru-NO-Pt@FA}

[0170] (1) N-GQDs@NH 2 (Surface Aminated N-GQDs Nanoparticles) Preparation

[0171] Weigh citric acid (40 mg), dissolve it in 40 mL of distilled water, add ammonia water (8 mL), and place the solution in a muffle furnace at 200° C. for 3 h. After cooling to room temperature, the pH was adjusted to 8 to obtain a light yellow solution, which was dialyzed in water for 4 h with a dialysis bag with a molecular weight cut-off of 1000, and the solution was rotary evaporated to obtain N-GQDs as a solid. Dissolve N-GQDs in 2.0 mL of distilled water, add EDC / NHS, activate for 1 h, add 1 mL of anhydrous ethylenediamine, and stir at room temperature for 24 h. The solution was dialyzed in water for 24 hours with a dialysis bag with a molecular weight cut-off of 1000, and the solution in the dialysis bag was freeze-dried to obtain the product N-GQDs@NH 2 .

[0172] (2) Preparation of nanoparticle composite dru...

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Abstract

The present invention provides nitric oxide and cisplatin targeted combined controllable drug delivery nano-medicine system, the structure is as follows: carrier-exogenous NO donor-metal complex; wherein, the carrier is a nano-carrier; the exogenous The source NO donor is a metal ruthenium nitrosyl NO donor; the metal complex is a platinum complex. The drug system has fluorescent tracers, can selectively target specific cancer cells, can deliver nitric oxide and cisplatin drugs under the control of near-infrared light, and has the function of photothermal therapy. Combined administration of nitric oxide and cisplatin and synergistic photothermal therapy to achieve highly effective anticancer effects.

Description

technical field [0001] The invention relates to the field of biology and the field of inorganic nano medicines. Specifically, the present invention provides a multifunctional bimetallic nanocomposite drug system with fluorescent tracer, targeted delivery, and intracellular near-infrared light photocontrol delivery of nitric oxide and cisplatin, and a preparation method thereof. Background technique [0002] Cis-dichlorodiammine platinum (II) (cisplatin, cisplatin) has been widely used in the chemotherapy of various cancers since it was discovered in the 1970s that it can inhibit the growth of tumor cells, and it plays an important role in chemotherapy drugs. Location. Mechanism of action of platinum: After entering the body, it acts on tumor cell DNA, coordinates with DNA to form an adduct, and inhibits DNA replication, thereby causing tumor cell apoptosis. [0003] Cisplatin is a first-line chemotherapy drug for several cancers, including ovarian, breast, bladder, head an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/52A61K47/69A61K49/00A61K41/00A61K33/00A61K33/243A61P35/00
CPCA61K41/0052A61K47/52A61K47/6923A61K49/0067A61P35/00A61K33/00A61K33/24A61K2300/00
Inventor 刘劲刚史淑文李延慧喻雅婷
Owner EAST CHINA UNIV OF SCI & TECH
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