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Sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent and preparation method thereof

A technology of Prussian blue and sodium nitroprusside, which is applied in the field of drug-loaded Prussian blue analogue nano-photothermal therapeutic agent and its preparation, can solve the problems of no reports, etc., achieve low price, excellent photothermal stability, and easy large-scale mass production Effect

Active Publication Date: 2018-11-13
CHONGQING MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is no report on the drug-loaded Prussian blue analogue nano-photothermal therapeutic agent conjugated with sodium nitroprusside and its preparation method.

Method used

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  • Sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent and preparation method thereof
  • Sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent and preparation method thereof
  • Sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0028] 1. Preparation of Sodium Nitroprusside Conjugated Prussian Blue Analog Nanoparticles (m-PB-NO)

[0029] Weigh 60 mg of potassium ferricyanide, 488.7 mg of sodium nitroprusside and 3 g of polyvinylpyrrolidone (PVP) in 40 mL of 0.1 M hydrochloric acid solution, stir for 20 minutes to disperse evenly. And it was transferred to a water bath, and stirred and reacted at 80° C. for 12 hours. The precipitate was collected by centrifugation and ultrasonically washed with water for 3 times to obtain the Prussian blue analogue nanoparticles conjugated with sodium nitroprusside.

[0030] 2. Preparation of drug-loaded Prussian blue analog nanoparticles conjugated with sodium nitroprusside (DTX@m-PB-NO)

[0031] Using docetaxel (DTX) as a model drug, 10 mg of sodium nitroprusside-conjugated Prussian blue analogue nanoparticles were dispersed in 10 mL of water, 1 mL of 1.5 mg / mL docetaxel ethanol solution was added, and the reaction was stirred for 12 hours. The mixed solution obtai...

Embodiment 2

[0034] The m-PB-NO prepared in Example 1 was dispersed in water to form a 0.2 mg / mL suspension, and 1 mL of the suspension was placed in a quartz cuvette. Use power density of 0.8W / cm 2 , 1.0W / cm 2 , 1.5W / cm 2 , 2.0W / cm 2 , 2.5W / cm 2 The 808nm laser was irradiated for 10 minutes respectively, and the temperature changes at different time points were recorded by using a thermocouple probe thermometer. Figure 4 As shown, as the irradiation time prolongs, the temperature of the solution increases gradually, and at the same time, as the laser power increases, the solution temperature rise rate increases. When the laser power is 2.5W / cm 2 , the temperature of the solution rose to 63.4 °C, indicating that m-PB-NO has excellent photothermal conversion efficiency.

Embodiment 3

[0036] Take the m-PB-NO prepared in Example 1 and disperse it in water, take 0.05mg / mL, 0.1mg / mL, 0.2mg / mL, 0.5mg / mL, 1mg / mL m-PB-NO suspension 1mL In a quartz cuvette, use water as a blank control. Use power density of 0.8W / cm 2 The 808nm laser was irradiated for 10 minutes respectively, and the temperature changes at different time points were recorded by using a thermocouple probe thermometer. Figure 5 As shown, as the irradiation time prolongs, the temperature of the solution increases gradually, and at the same time, with the increase of the concentration of m-PB-NO, the temperature of the solution increases faster. When the concentration of m-PB-NO is 1mg / mL, the temperature of the solution It increased to 47.5℃, indicating that m-PB-NO has excellent photothermal conversion efficiency.

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Abstract

The invention discloses a sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent and a preparation method thereof. The particle size of the sodiumnitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent prepared by a hydrothermal reaction method is 205.4nm, and passive targeting can be achieved by means of an enhanced permeability and retention (EPR) effect of a tumor site. Under the illumination of near-infrared laser, the nano-photothermal therapeutic agent can not only induce photothermal ablation of tumor cells through excellent photothermal conversion efficiency, but also can control NO release, thereby improving the EPR effect and increasing intratumoral delivery of nanoparticles. Furthermore, the NO can also inhibit tumor progression by inducing apoptosis of the tumor cells, preventing angiogenesis, reversing multidrug resistance, and the like. On the other hand, due to the structural difference between sodium nitroprusside and potassium ferricyanide, the lattice defects of the nanoparticles are caused, and the drug loading capacity of the nano-photothermal therapeutic agent is accordingly increased. Therefore, after chemotherapeutic drugs are carried, under the irradiation of near-infrared light, the nano-photothermal therapeutic agent can realize dose-controlled NO release and phototherapy and chemotherapy combined oncotherapy. In addition, the sodium nitroprusside-conjugated medicine-carrying prussian blue analogue nano-photothermal therapeutic agent provided by theinvention also has good photothermal stability and certain photoacoustic contrast properties.

Description

technical field [0001] The invention relates to the field of medical medicine, in particular to a drug-loaded Prussian blue analog nanometer photothermal therapeutic agent conjugated with sodium nitroprusside and a preparation method thereof. Background technique [0002] Nitric oxide (NO) is an important signaling molecule produced endogenously by nitric oxide synthase. It plays a vital role in various biological systems including cardiovascular, nervous, respiratory, gastrointestinal and immune. In recent years, the effect of NO on tumor proliferation, apoptosis and metastasis has gradually attracted people's attention. Notably, the antitumor effect of NO strongly depends on its concentration at the target site. For example, picomolar NO promotes tumor progression by stimulating tumor cell growth and enhancing angiogenesis, while micromolar NO inhibits tumor progression by inducing tumor cell apoptosis, preventing angiogenesis, and reversing multidrug resistance. Theref...

Claims

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Application Information

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IPC IPC(8): A61K41/00A61K31/337A61K33/00A61K9/14A61K49/22A61P35/00
CPCA61K9/14A61K31/337A61K33/00A61K41/0052A61K49/225A61P35/00A61K2300/00
Inventor 张良珂冯滔
Owner CHONGQING MEDICAL UNIVERSITY
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