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Multi-functional stimuli sensitive polymer-gold nanocage carrier and preparation method thereof

A stimulus-sensitive, nano-gold technology, applied in the fields of polymer chemistry and biomedical engineering, can solve the problems of great toxicity, killing large normal cells, and lack of specificity, and achieve low toxicity, good photothermal conversion effect, The effect of broad application value

Inactive Publication Date: 2015-01-07
SUN YAT SEN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, anti-tumor drugs are still the main method for clinical treatment of tumors, but the application of anti-tumor drugs has many defects: most of them have great toxicity, lack of specificity, and will kill a large number of normal cells while killing tumor cells
At present, there is a lack of multifunctional gold nanocarriers that can simultaneously achieve chemotherapy, hyperthermia and precise positioning in the prior art

Method used

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  • Multi-functional stimuli sensitive polymer-gold nanocage carrier and preparation method thereof
  • Multi-functional stimuli sensitive polymer-gold nanocage carrier and preparation method thereof
  • Multi-functional stimuli sensitive polymer-gold nanocage carrier and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] The synthesis of embodiment 1 polymer

[0052] (1) The synthesis of benzyl aspartate, the reaction mechanism and reaction process are as follows:

[0053]

[0054] Take a 500 mL one-mouth eggplant-shaped flask, add 100 mL of anhydrous ether, and then add 10 mL of H 2 SO 4 (98%), stirring while adding, after cooling to room temperature, add 100 mL benzyl alcohol (1 mol, 1.04 g / mL, 108.06 g / mol), stir well, and spin distill off ether. A total of 13.3 g (0.1 mol, 133.04 g / mol) of L-aspartic acid was added several times. After stirring and reacting at room temperature for 24 h, 200 mL of 95% ethanol was added, and then 50 mL of pyridine was added dropwise, stirring vigorously while dropping. Then put it in the refrigerator to freeze overnight, filter with suction, wash the filter cake with ultrapure water several times, and then wash twice with anhydrous ether. Drain, place in a 500 mL Erlenmeyer flask, add 300-400 mL of water, heat and stir at 70 °C to dissolv...

Embodiment 2

[0072] Example 2 Polymer self-assembled into micelles

[0073] Take 50 mg of the amphiphilic, diblock polymer PAsp(MEA)-PAsp(DIP) prepared in Example 1 and dissolve it with DMSO, then disperse it in a solution of about 50 mLPBS=8.0, and ultrasonically through the ultrasonic crushing instrument, Self-packed as micelles, dialyzed, and then filtered the micellar solution through a 450 nm filter membrane, protected the micellar solution with nitrogen gas, and removed impurities by ultrafiltration with an ultrafiltration tube with a molecular weight of 100,000. Its structure is as figure 1 ,from figure 1 It can be seen that the main NMR peaks have a good assignment, indicating that PAsp(DIP)-PAsp(MEA) has been successfully prepared.

[0074] The morphology of the prepared polymer micelles was characterized by PhihPsCM120 electron microscope with an excitation voltage of 60 KV. The sample preparation method is as follows: drop 10 μL (concentration: 1 mg / mL) of the sample soluti...

Embodiment 3

[0075] Example 3 Preparation of mPEG-bPEI-LA

[0076] (1) Synthesis of monomethyl ether polyethylene glycol-carbonyl imidazole (mPEG-CDI)

[0077] The reaction scheme is as follows, 4.0 g of monomethyl ether polyethylene glycol (mPEG-OH) was added into a two-necked flask, dried in vacuum at 50°C for 4 h, dissolved in 30 mL of tetrahydrofuran, and 3.2 g (10 eq.) of N,N- Carbonyldiimidazole (CDI), protected by argon, reacted at room temperature for 24 h, precipitated in a large amount of anhydrous ether, filtered and dried to obtain a white powder product with a yield of 85%.

[0078]

[0079] (2) Synthesis of monomethyl ether polyethylene glycol grafted polyethyleneimine (mPEG-bPEI)

[0080] The reaction scheme is as follows, 1.1 g PEI was added to a 50 mL two-neck flask, 20 mL of chloroform was added to dissolve it, and then 800 mg of mPEG-CDI (10 eq.) was added, and the reaction was stirred at room temperature for 24 h, and the dialysis bag (MWCO = 3.5 kDa) was dialyze...

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Abstract

The invention belongs to the field of high polymer chemistry and biomedical engineering, and particularly relates to a multi-functional stimuli sensitive polymer-gold nanocage carrier and a preparation method thereof. The multi-functional carrier has a nucleus-shell-crown structure formed by a nucleus, a shell and a crown; the nucleus is formed by polymeric micelles, the shell is formed by gold nanocages, and the crown is formed by methoxy polyethylene glycol-branched polyethylenimine-lipoic acid; and the nano-carrier has a good photothermal conversion effect on the condition of 808 nm. The carrier has low toxicity for cells and can bear not only drugs but also genes or nucleic acids, thereby achieving the integration of carrier positioning, chemotherapy, thermal therapy and gene therapy and having a wide application value.

Description

technical field [0001] The invention belongs to the field of polymer chemistry and biomedical engineering, and more specifically relates to a multifunctional stimulation-sensitive polymer-nano gold cage carrier and a preparation method thereof. Background technique [0002] With the improvement of living conditions and the continuous change of social environment, the diseases that threaten human beings are more diverse, among which tumors are getting more and more attention. Early diagnosis and effective treatment of tumors are the key measures to improve the survival rate of cancer patients. At present, anti-tumor drugs are still the main method for clinical treatment of tumors, but the application of anti-tumor drugs has many defects: most of them have great toxicity, lack of specificity, and will kill a large number of normal cells while killing tumor cells . [0003] In order to improve the accuracy of early cancer detection and diagnosis, people are committed to the re...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/34A61K47/02A61K48/00A61P35/00C08G69/48C08G81/00
Inventor 帅心涛周国永程度王露肖洪黄毅
Owner SUN YAT SEN UNIV
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