A tumor-targeted composite nano drug carrier, drug, preparation method and application
A nano-drug carrier, tumor-targeting technology, applied in anti-tumor drugs, drug combinations, pharmaceutical formulations, etc., can solve the problems of exogenous stimulation, difficult to improve delivery efficiency, etc., to achieve accelerated release, reduced oxidation, and efficient killing. Effect
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Embodiment 1
[0040] Example 1: Preparation steps of composite nano drug carrier
[0041] Preparation of nano-hydrogel Dissolve 0.71g Tween-80 and 0.82g Span-80 in 20mL n-hexane, and dissolve 162mg 2-aminoethyl methacrylate hydrochloride (AMA) in 300mg water; 13.9mg Poly(ethylene glycol) diacrylate (PEGDA); 10.8 mg Potassium persulfate (KPS). After mixing the two solutions, pass nitrogen to remove oxygen, stir and heat at 60°C, react for 2 hours, and cool to room temperature. The sample was precipitated by adding tetrahydrofuran dropwise, collected by centrifugation, washed three times with tetrahydrofuran, and dialyzed for 24 hours to obtain nanogel nanogel.
[0042] Nanohydrogel modification Add 0.5mL 1g / mL 1-iodohexadecane to the nanohydrogel product obtained in the above steps, let it stand for layers, and add 100uL 0.1g / mL docosanoic acid to the supernatant (dichloromethane dissolved), stirred for 3h. Use EDC / NHS to activate each for 30min (400mg / ml, 200mg / ml, take 200ul). Add 400ul o...
Embodiment 2
[0053] Example 2: Using Targeted Nano Drug Carriers to Treat Tumor Cells
[0054] Make targeted nano-drug carrier according to Example 1;
[0055] An appropriate amount of targeted drug delivery carrier was co-cultured with tumor cells for 72 hours, the cell death rate was investigated, and the biocompatibility of the carrier was evaluated. The carrier for targeted drug delivery of the present invention has good biocompatibility.
[0056] Add 100 μL of 10 μg / ml Dox and 10 μM ferrous sulfate to the carrier for targeted drug delivery prepared by the method in Example 1, and incubate for 6 hours to obtain an anti-tumor targeted drug.
[0057] Hela cells in the exponential growth phase were cultured in a six-well culture plate, and 5 μL of the drug-loaded product (targeted anti-tumor drug) was added to each well, and incubated for 24 hours.
[0058] The killing effect of drug-loaded products on Hela was investigated under the FITC / PI double staining model by flow cytometry. The...
Embodiment 3
[0059] Example 3: Using targeted nano-drug carriers to treat tumor models in vivo
[0060] Make targeted nano-drug carrier according to Example 1;
[0061] Drug loading: add 100 μL, 10 μg / ml Dox, 10 μM ferrous sulfate to the carrier for targeted drug delivery obtained by the method of Example 1, and incubate for 6 hours to obtain an anti-tumor targeted drug;
[0062] The injection method is: 60 μL for each injection, once every 72 hours, and a total of 7 injections. The body weight and tumor volume (measured in vitro) were observed daily, and the tumors in the mice were dissected after 7 injections.
[0063] image 3 Two mice in the middle, normal mice on the left and tumor-bearing mice on the right. After injecting the targeted drug carrier (labeled with rhodamine) through the tail vein, the tumor sites of the tumor-bearing mice can be seen to be significantly enriched effect.
[0064] Figure 4 The tumor-bearing mice targeted in the above were divided into three groups:...
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