Preparation And Anti-Tumor Study Of Doxorubicin Loaded Gold Nanoparticle Drug Carrier System

Based on the fact that nano-drug delivery system is widely studied with many advantages,and the physical and chemical properties of gold nanoparticles,including their uniformity,stability,water solubility and biocompatibility,make them suitable for in vivo research applications,gold nanoparticles are selected as drug delivery agents for research.Three kinds of gold nanoparticles were prepared for comparison due to their different shapes and sizes.Doxorubicin,as a broad-spectrum anticancer drug,has anticancer activity against a variety of tumor cells.Hyaluronic acid is also used for modification because of its good water solubility and biocompatibility in vivo,and it can be used to target tumor cells rich in CD44 receptors and cell migration receptors with drug delivery system.Therefore,three different gold nanoparticle drug delivery systems were synthesized and their antitumor activities were compared.In this project,three kinds of gold nanoparticles with different shapes and particle sizes were synthesized by seed growth method.The synthesis results of nanoparticles were verified by dynamic light scattering instrument,ultraviolet spectroscopy and transmission electron microscope images.The HA-Dox complex was synthesized,verified by infrared spectrum and thermogravimetric experiment,and the zeta potential of the complex was measured at the same time.The drug was loaded onto the gold nanoparticles through electrostatic binding,and the best binding prescription process was screened by orthogonal experiments.The drug release characteristics of the drug delivery systems were determined by in vitro release experiments.The cytotoxicity tests were performed by MTT assay.Pharmacokinetic experiments were conducted to analyze and compare the in vivo utilization of the drug loading systems.Meanwhile,the tumor growth curve and tumor inhibition index of S180 tumor-bearing mice were used to compare the tumor inhibition degree of the drug delivery systems.The safety and efficacy of the drug delivery system was further determined by observing the pathological sections of organs and tumor tissues of mice with tumor.The results showed that three different types of gold nanoparticles were successfully synthesized,namely Au NPs 1 with an average particle size of 14.96 nm,and Au NPs 2 with an average particle size of 39.80 nm,Au NRs with a length diameter of 40 nm and a width diameter of about 15 nm and a aspect ratio of about2.67.The HA-Dox complex with zeta potential of-29 m V was synthesized,and the optimal prescription was obtained: the dosage of HA-Dox was 15 mg,and the reaction was stirred at 30 ℃ for 6 h.Under this condition,three kinds of gold nanoparticle drug delivery systems were obtained.The drug release results in p H 6.5and p H 7.4 PBS buffered solution show that the drug loading systems were more likely to release drugs under the mimic environment of tumor cells and were slightly stable under the normal body fluid environment.The cumulative release order at 72 h from large to small is Au NPs2/HA-Dox,Au NRs/HA-Dox and Au NPs1/HA-Dox.The results of the cytostatic rate experiment showed that for normal cells HEK293,the synthetic drug-loading systems were less toxic,while for the three tumor cells Hep G2,S180 and HT29,the systems were highly toxic.The order of inhibitory rates of preparations carrying the same amount of drugs from large to small is Au NPs2/HA-Dox,Au NRs/HA-Dox and Au NPs1/HA-Dox.The results of pharmacokinetic experiments are that the three drug-loading systems have higher bioavailability than the drug alone after injection into the rat via tail vein.And the results of tumor inhibition experiments in S180 tumor-bearing mice showed that the drug loading systems had better tumor inhibition effect and their order is Au NPs2/HA-Dox>Au NRs/HA-Dox>Au NPs1/HA-Dox.Based on the above experimental results,we concluded that the synthesized Au NPs1/HA-Dox,Au NPs2/HA-Dox,and Au NRs/HA-Dox have a large drug loading,and the drug release effect is better under slightly acidic conditions.They can also target more tumor cells and has stronger cytotoxicity than normal cells.The bioavailability and anti-tumor effect in vivo are also better in the three drug-loading systems and the anti-tumor activity sequence is Au NPs2/HA-Dox>Au NRs/HA-Dox>Au NPs1/HA-Dox.