A kind of nanocarboxylase containing hypoxia-activated prodrug and its preparation method and application
A nano-cluster and prodrug technology, applied in the field of medicine, can solve the problems of cancer cell starvation therapy failure, lethal chain reaction, off-target effect, etc. simple effect
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
preparation example Construction
[0060] The present invention also provides a method for preparing the above-mentioned nanocarboxylase containing hypoxia-activated prodrug, comprising the following steps:
[0061] A) Mix 2-carboxyethyl-3-methylmaleic anhydride with PEG-b-PHEMA in a pyridine solution for reaction, and obtain PEG-b-PHEMA after purification of the reaction product CMA ;
[0062] B) Combining the dual enzyme cascade with PEG-b-PHEMA CMA Mix and dissolve in PBS buffer, incubate and centrifuge to obtain the inner core;
[0063] C) Resuspend the inner core, add bovine serum albumin and bovine serum albumin grafted hypoxia-activated prodrug and PEG-b-PHEMA according to the desired ratio CMA , to react to obtain nanocarboxylase containing hypoxia-activated prodrug.
[0064] The present invention first prepares PEG-b-PHEMA CMA , the PEG-b-PHEMA CMA It is a polyethylene glycol-b-poly(2-hydroxyethyl methacrylate) block copolymer modified by 2-carboxyethyl-3-methylmaleic anhydride, and the preparatio...
Embodiment 1
[0095] Embodiment 1, block copolymer PEG-b-PHEMA CMA Synthesis:
[0096] (1) First prepare 2-carboxyethyl-3-methyl maleic anhydride (CMA):
[0097] Add triethyl 2-phosphonic acid propionate (19.5 g, 69.5 mmol) to a THF (200 mL) suspension containing sodium hydride (1.4 g, 58 mmol) in a cold bath at 0° C. 2 Gas is no longer produced. Dimethyl 2-oxoglutarate (7.5 g, 43 mmol) was added to the previously reacted mixed solution and stirred at 0° C. for 30 minutes, after which saturated aqueous ammonium chloride (200 mL) was added to the reaction solution to End the reaction. The obtained crude product was extracted with diethyl ether, and the diethyl ether was removed using a rotary evaporator, and the mixture was refined and purified by silica gel column chromatography (ethyl acetate / n-hexane=1 / 10 (V / V), Rf=0.7) to obtain a yellow oil. The resulting yellow oil was dissolved in a mixture of ethanol (180 mL) and 2M aqueous KOH (100 mL) and refluxed for 1 h. After cooling to room...
Embodiment 2
[0102] Example 2, BSA TPZ Synthesis:
[0103] (1) Add 2 mL of succinic anhydride (25 mg, 0.25 mmol, 33 equivalent) solution, after which the pH of the solution was adjusted to 9.3 using sodium hydroxide solution. The solution was then stirred at room temperature for 18 hours, and then dialyzed against 0.01 M triethylamine aqueous solution. The overnight dialyzed sample was lyophilized to obtain fluffy BSA SA White powder (120mg).
[0104] (2) At 0°C, the BSA SA (50 mg) and EDC (7.1 mg, 3.7 mmol) were dissolved in 5 mL of 0.1 M sodium bicarbonate buffer (pH=8.8) for reaction. After 5 minutes, TPZ (4.5 mg, 2.5 mmol) was added and stirred at room temperature overnight. Remove water and free TPZ by ultrafiltration (cut-off Mw=10,000) centrifugal purification to obtain BSA TPZ . see Figure 7-9 , Figure 7 For BSA in Example 1 TPZ The synthetic flow chart of Figure 8 It is the ultraviolet-visible light absorption spectrum figure of TPZ among the embodiment 1; Figure 9...
PUM
| Property | Measurement | Unit |
|---|---|---|
| size | aaaaa | aaaaa |
| size | aaaaa | aaaaa |
| thickness | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More