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ROS (reactive oxygen species)-response nano drug delivery system as well as preparation method and application thereof

A delivery system and nano-drug technology, applied in the field of nano-drug delivery system and its preparation, can solve the problem of little research on drug release, and achieve the effects of good stability, uniform particle size and good biocompatibility

Active Publication Date: 2016-06-01
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such as pH-sensitive, reduction-sensitive, temperature-sensitive, enzyme-sensitive and light-sensitive, etc., but the drug release in response to reactive oxygen species (ROS) is rarely studied

Method used

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  • ROS (reactive oxygen species)-response nano drug delivery system as well as preparation method and application thereof
  • ROS (reactive oxygen species)-response nano drug delivery system as well as preparation method and application thereof
  • ROS (reactive oxygen species)-response nano drug delivery system as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] 1. The synthesis steps of up-conversion material UCNPs are as follows:

[0055] 4 mmol CF 3 COONa and 2mmol (total amount) Ln(CF 3 COO) 3 (Ln: 78mol%Y+20mol%Yb+1.6mol%Er+0.4mol%Tm) was added to a 100mL three-necked bottle, and 20mL oleylamine was added. Stir and heat to 120°C to remove moisture and oxygen, and stir for 1 h with nitrogen gas. During this period, the state of nitrogen gas has been kept, and when the reaction solution turns transparent, the temperature is raised to 320°C, and the temperature rises by 10°C per minute. After rising to 320°C, the reaction was stirred for 1 hour, and the reaction ended. When the temperature dropped to room temperature, excess oleylamine was washed away with hexane oxide and chloroform, and vacuum-dried.

[0056] 2. The steps of synthesizing ROS-sensitive thioketal linker (TL) are as follows:

[0057] Anhydrous 3-mercaptopropionic acid (5.2g, 49.1mmol) and anhydrous acetone (5.8g, 98.2mmol) were saturated with dry HCl gas...

Embodiment 2

[0064] 1. The synthesis steps of the up-conversion material UCNPs are the same as in Example 1, and will not be repeated here

[0065] 2. The steps of the ROS-sensitive thioketal linker (TL) are the same as those in Example 1, and will not be repeated here.

[0066] 3. The experimental steps of synthesizing TL-DOX are as follows:

[0067] TL (252.1mg, 1.0mmol) was dissolved in anhydrous 10mL DMF, and triethylamine (TEA, 303.6mg, 3.0mmol) and 2,4,6-trichlorobenzoyl chloride (241.9mg, 1.0mmol) were added in sequence, Dimethylaminopyridine (DMAP, 24.4 mg, 0.2 mmol), stirred for 10 min. Doxorubicin (DOX, 271.76 mg, 0.5 mmol) dissolved in 10 mL of DMF was then added, and the reaction was stirred at room temperature for 24 h. The reaction was quenched with water, and the crude product was passed through a silica gel column to obtain pure product.

[0068] 4. The process of assembling Ce6-DOX-UCNPs is as follows:

[0069] Add TL-DOX (0.06mmol), mPEG-COOH (0.15mmol) and UCNPs (10m...

Embodiment 3

[0071] 1. The synthesis steps of UCNPs, an up-conversion material, are the same as those in Example 1, and will not be repeated here.

[0072] 2. The steps of the ROS-sensitive thioketal linker (TL) are the same as those in Example 1, and will not be repeated here.

[0073] 3. The experimental steps for synthesizing TL-CPT are the same as those in Example 1, and will not be repeated here.

[0074] 4. The process of assembling PheA-CPT-UCNPs is as follows:

[0075] TL-CPT (0.06mmol), PheA (0.06mmol), mPEG-COOH (0.15mmol) and UCNPs (10mg) were added to 3mL DMF, 150W ultrasonic for 15min, stirred at room temperature for 1h and centrifuged three times (11250g, 10min / time) to collect solid matter , washed with HEPES buffer solution and resuspended.

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Abstract

The invention discloses a ROS (reactive oxygen species)-response nano drug delivery system which comprises UCNPs (upconversion nanophosphors), carboxylated PEG (polyethylene glycol) connected with UCNPs, a photosensitizer, a ROS-sensitive thioketal linker and an anti-tumor chemotherapeutic drug connected with the thioketal linker, wherein the photosensitizer contains carboxyl, and the excitation spectrum of the photosensitizer is superposed with the upconversion emission spectrum of UCNPs. The invention also discloses a preparation method and application of the ROS-response nano drug delivery system. The ROS-response nano drug delivery system disclosed by the invention can control the drug release temporally and spatially and can perform combination therapy of photodynamics therapy and chemotherapy to eradicate tumor once; and meanwhile, the fluorescence emitted by UCNPs or the light emitted by the photosensitizer can perform fluorescence imaging, and thus, therapy-imaging integration can be realized.

Description

technical field [0001] The invention relates to the field of pharmaceutical preparations, in particular to a ROS-responsive nano drug delivery system and its preparation method and application. Background technique [0002] Chemotherapy is a common treatment method after tumor diagnosis, but chemotherapy is often accompanied by many side effects. In order to obtain the best therapeutic effect and avoid side effects, many nanomaterials are used to load slow-release chemotherapy drugs. These drugs are usually tumor-targetable and the drug release is controlled. Such as pH-sensitive, reduction-sensitive, temperature-sensitive, enzyme-sensitive and light-sensitive, etc., but the drug release in response to reactive oxygen species (ROS) is rarely studied. Light-controlled ROS stimulation has the advantage of being able to precisely control the time and location of release. [0003] The ROS pressure of tumor cells is higher than that of normal cells, partly due to the stimulatio...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/48A61K49/00A61P35/00A61K31/4745A61K31/704
CPCA61K31/4745A61K31/704A61K41/0071A61K49/0019A61K49/0036A61K49/0054A61K2300/00
Inventor 崔大祥岳彩霞
Owner SHANGHAI JIAO TONG UNIV
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