Design, Synthesis And Biological Activity Of Gold Nanoparticles Drug Delivery System

Recent years,cancer has been a high incidence trend,drug treatment has always been the main way of treating such diseases.However,chemotherapy drugs have large side effects and drug resistance,which reduces their therapeutic effects.Due to its special physical properties and excellent biocompatibility,gold nanoparticles can be used as a drug carrier to deliver drugs,which releases drugs in the lesion area.Thus,increasing the utilization rate of drugs overcoming drug resistance,reducing toxic side effects,and make nanoparitcles have broad prospects in the medical field.Gold nanoparticles are widely used as a variety of drug carriers which are modified easily with Hyaluronic acid and folic to achieve the role of targeting cancer cell.Hyaluronic acid(HA)is an acid mucopolysaccharide,which can be specifically recognized by CD44 receptor due to its non-toxicity and biodegradability,and has rich chemical modification functional groups.Therefore,the antitumor drugs can be combined with the modification of gold nanoparticles to enhance the antitumor effect of drugs.Folic acid(FA)is a water-soluble vitamin that is essential for the body,which is also a targeting agent.Many cancer cell lines overexpress folate receptors due to their rapid growth and cell division.Therefore,gold nanoparticle is modified by FA to enhance its tumor targeting.Based on the physical and biological properties of gold nanoparticles,the following aspects are studied:1?Gold nanoparticle with the size of 15 nm,have special properities for uniform dispersion by boiling with deionized water,and then modify them by attaching hyaluronic acid(HA),polyethylene glycol(PEG),adipic dihydrazide(ADH),and the antitumor drug doxorubicin(DOX)is loaded through a chemical bond,and gold nanocomposites Au@MPA-PEG-HA-ADH-DOX is obtained,which can be well dispersed in an aqueous solution.It was characterized by Transmission electron microscope(TEM),Zeta potential analyzer,UV-visible spectrophotometer,the biological activity of gold nanocomposites by MTT in vitro,which are used to detect the effects of gold nanocomposites on Hela,HepG2,HCT-116 and QSG-7701 cells.The results show that gold nanocomposites were slightly toxic to cells under high dose conditions.The toxicity of gold nanocomposites are significantly enhanced.Cellular uptake experiments have shown that gold nanoparticles can be modified by hyaluronic acid which more easily to enter Hela,HCT-116 cells with a large number of CD44 receptors,The nanocomphsites were tested by flow cytometry,fluorescent inverted microscope,high content imaging analysis system,etc.It found that nanocomphsites have a function of reduction of and the mitochondrial membrane potential and increasing the reactive oxygen species to promote apoptosis.2?We modified the gold nanoparticles with folic acid and polyethylene glycol,and then modified the drug to obtain the gold nanocomposites Au@MPA-PEG-FA-PTX by paclitaxel successfully.Characterization by Transmission electron microscope(TEM),Fourier transform infrared spectroscopy,Ultraviolet-visible spectrophotometer,which showed the nanomaterials were well modified,and then tested by MTT assay.Particularlly,gold nanoparticles modified by folate have a good targeting effect for tumors.The apoptosis and autophagy experiments showed the modified gold nanoparticles had better pharmacological effects than PTX,such as inhibiting autophagy and increasing apoptosis of tumor cells,and improving the therapeutic effect.