▎ 摘 要
NOVELTY - Method for preparing a smart responsive nanoparticle having a targeted photothermal effect involves preparing a liposome film having pH sensitivity by using carboxylated cholesterol and egg yolk lecithin, preparing hydrogel prepolymer aqueous solution using liposome film as a polymerization template, temperature sensitive isopropyl acrylamide as monomer, and N,N-methylenebisacrylamide as a cross-linking agent by performing template in situ polymerization method, reacting the graphene oxide with folic acid, 1-ethyl-(3-dimethylaminopropyl)carbodiimide, and nitrogen-hydroxysuccinimide to obtain folic acid-modified graphene oxide, and loading the folic acid-modified graphene oxide onto the liposome gel to obtain the final product. USE - The method is useful for preparing a smart responsive nanoparticle having a targeted photothermal effect, which is used for performing cancer cell therapy. ADVANTAGE - The method prepares smart responsive nanoparticle, which has synergistic effect of targeting, tumor hyperthermia and chemotherapy in the later stage, and increases the stability of the polymer material. DETAILED DESCRIPTION - Method for preparing a smart responsive nanoparticle having a targeted photothermal effect involves (a) taking 40-50 mu mol egg yolk lecithin and 13-15 mu mol cholesterol succinic acid monoester, dissolving with 2-4 ml chloroform, removing the solvent by performing rotary evaporation, obtaining a colorless and translucent film, and drying in a vacuum to obtain a dried liposome film, (b) taking 500-550 mg isopropyl acrylamide, 50-55 mg N,N-methylenebisacrylamide, 5-8 mg azobisisobutylphosphonium hydrochloride and 260-280 mmol ammonium sulfate, and dissolving in 5-8 ml deionized water to prepare a hydrogel prepolymer aqueous solution, (c) detaching the dried liposome film by using hand to dissolve into the aqueous solution of the hydrogel prepolymer, and ultrasonicating in an ice water bath to form a mixed solution comprising a liposome vesicle and a nanogel prepolymer aqueous solution, (d) adding 50-70 mg ascorbic acid to the mixed solution, vacuuming, introducing nitrogen gas, repeating 3-5 times, transferring to a nitrogen atmosphere sealed reaction device, reacting in a 45-50 degrees C water bath for 70-90 minutes, and dialyzing to remove unreacted impurities from the solution in a dialysis bag, (e) successively dialyzing the obtained solution with a 200 nm and 100 nm pore size liposome extruder to obtain a double sensitive liposome nanogel solution, (f) adding 50-60 mg graphene oxide with 50-60 ml distilled water, and ultrasonically shaking under ice bath conditions to peel off the graphite oxide sheet to obtain a brown-yellow dispersion, centrifuging the dispersion at 1000-12000 revolutions per minute (rpm) for 15-25 minutes, collecting the brownish yellow supernatant, adding the precipitate to the distilled water again, repeating the above steps, and combining the supernatant to obtain an aqueous graphene oxide solution, (g) dialyzing the aqueous graphene oxide solution with distilled water, and obtaining the filtrate as a purified graphene oxide dispersion, (h) uniformly dispersing the graphite oxide dispersion by ultrasonication, adding 5-7 g sodium hydroxide and 5-7 g sodium hypochlorite, converting the hydroxyl group on the graphene oxide sheet into a carboxyl group by an ultrasonic bath for 1-3 hours, after the reaction is completed, neutralizing with dilute hydrochloric acid and repeatedly rinsing, collecting the upper black solution after centrifugation, and dialyzing against deionized water for 40-50 hours to remove unreacted water-soluble substances, (i) adding 0.5-0.8 g folic acid to the obtained solution, uniformly dispersing ultrasonically, and adding 125-127 mg 1-ethyl-(3-dimethylaminopropyl)carbodiimide and 182.5-184.5 mg nitrogen-hydroxysuccinimide while stirring, ultrasonicating for 2-3 hours, dialyzing with sodium bicarbonate solution of pH 7.8-8.2, changing water every 3-5 hours, and completing dialysis after 40-50 hours to obtain a black solution, (j) removing the water in the black solution by rotary evaporation, repeatedly washing with acetone, and drying in vacuum to obtain folic acid-modified graphene oxide, and (k) mixing the folic acid-modified graphene oxide with the double-sensitive liposome nanogel solution under stirring condition in the dark for 8-12 hours, washing by centrifugation, and freeze-drying to obtain a final product.