Preparation,Characterization And Antitumor Property Of Gold Nanorods Modified Podophyllotoxin Liposomes

Podophyllotoxin(POD)is a phenyltetralin-type lignin isolated from roots and rhizomes of Podophyllum hexandrum.In recent years,researchers have focused more on its anticancer activity.The main mechanism of POD for anticancer effect is binding to tubulin and then preventing the formation of mitotic spindles during the G2/M phase of cell division.However,the practical application of POD for cancer therapy was unsatisfactory due to its poor aqueous solubility and serious side effects.During the past few decades,liposome based nano-drug delivery systems have been successfully designed and fabricated to improve the efficiency of chemotherapeutics.However,conventional liposomal drug delivery is uncontrollable,and chemotherapy alone can not achieve therapeutic effects.Therefore,our group prepared nanocomposites GLP with gold nanorod-based liposomal podophyllotoxin,and in the near-infrared(NIR)light irradiation,tumor suppression is achieved by photothermal-chemotherapeutic synergy as well as thermo-photothermal controlled release.The results are as follows:(1)In this study,POD liposomes were prepared by membrane hydration method,and the preparation conditions were optimized by response surface methodology.The optimal preparation conditions were as follows: ratio of cholesterol to lecithin(w: w)3.6:40,ratio of lipid to drug(w:w)15.8:1,and the ultrasonic intensity 35(%),under the optimal conditions,the experimental encapsulation efficiency(EE)of POD liposome was 90.425%.On this basis,the POD liposomes were characterized by dynamic light scattering and TEM,and the POD liposomes with good dispersibility,uniform size,suitable Zeta potential and round shape were obtained.(2)Gold nanorod-based liposomal podophyllotoxin(GLP)were prepared by attaching GNRs@PSS@PLL to the surface of PEG-modified liposomes through electrostatic interaction.The basic characterization of GLP was carried out by different detection equipment.The obtained liposomes were uniformly covered by gold nanorods on the surface and had good stability.Fluorescence results showed that LP had stronger fluorescence intensity than POD.And GLP has the maximum absorption intensity at 808 nm,which can achieve maximum photothermal conversion efficiency.The results of photothermal test displayed that GLP has good photothermal stability and can rapidly heat up to 42 ? in a short time at a concentration of 100?g/m L,according to Roper's method,the photothermal conversion efficiency was calculated to be 46.1%.The results of photothermal control release experiments indicated that GLP had a higher release ability of photothermal controlled release than that of natural release,and the controlled release of GLP was achieved while drug concentration increased in tumor site,so as to achieve better therapeutic effect.(3)The cytotoxicity of gold nanorods liposomes(GL)was investigated by hemolysis test and MTT assay.The results demonstrated that GL had good biosafety.4T1 cells as a tumor cell model,the inhibitory effect of LP and POD on tumor was measured respectively,the results showed that the antitumor activity of POD liposomes was stronger than that of bare drug because LP has good water solubility,in which the lipid bilayer can effectively fuse the cell membrane and increase the intracellular POD activity;moreover,the killing effect of LP on 4T1 cells was concentration-dependent and timedependent.In addition,4T1 cells could effectively ingest GLP;The result of photothermal synergistic therapy indicated that the inhibitory rate of GLP through the combination therapy exceeded the sum of single chemotherapy and single photothermal therapy.Due to the external NIR stimulus,the gold nanorods on the surface of liposomes was converted optical energy into thermal energy;So that the lipidic phospholipid bilayer from gelatinous state into the liquid crystal state,thereby,drug rapid release was fulfilled,concentration of podophyllotoxin was increased as well as achieved tumor suppression effect.For vivo biodistribution and anti-tumor assays,the results manifested that there is a significant accumulation of GLP in the tumor area,and the tumor area shows a potent NIR-thermal effect after NIR irradiation.GLP,as a podophyllotoxin nanocarrier,can improve its solubility,effectively taken up by tumor cells,enhances the antitumor activity through the photothermal effect and enhances the antitumor activity finally.Therefore,it is potential for growth in the clinical treatment of cancer.