The Construction And Application Of A Tumor-targeting Near-infrared Laser-triggered Drug Delivery System Based On GO@Ag Nanoparticles

Light-sensitive nanocarriers are attracting increasing attention in biomedicalfield due to their advantages of high efficiency, controllability and specificity.Light-sensitive drug delivery system can purposefully regulate the release of drugs toincrease their selectivity to the target tissue and reduce the toxicity of chemotherapydrugs, thus it can improve the antitumor activity of the drugs.In this study, we developed doxorubicin (DOX)-loaded near-infrared (NIR)light-responsive drug delivery system based on GO@Ag. Firstly Ag nanoparticles(~10nm) were chemically deposited onto the surface of GO to get GO@Agnanocomposites. Then DOX was covalently conjugated onto GO@Ag by an esterbond. In the connection of DSPE-PEG2000-Maleimide(DPM), DSPE-PEG2000wasconnected to GO@Ag-DOX through the dispersing effect of DSPE extremity toimprove the water-soluble; while the Maleimide was linked to NGR by additionreaction, resulting in tumor targeting NIR controlled drug delivery systemGO@Ag-DOX-NGR. The whole process was characterized by TEM,XRD, UV-Vis,FT-IR and DLS. The results showed that we built the water soluble GO@Ag-DOX-NGR drug delivery system successfully.We also studied the release of DOX from GO@Ag-DOX-NGR and its thermaleffect under the near-infrared light irradiation(NIR). Results indicated that DOXrelease can be externally triggered due to the lacalized surface plasmonresonances(SPR) of Ag nanoparticles under NIR light. The drug release profileshowed that3.5-fold higher DOX released under NIR light24h than in the dark.Besides, the temperature of GO@Ag-DOX-NGR solution was higher than GO byabout10℃after irradiated5min under2W/cm2NIR.In vitro experiments, we chose breast cancer cells MCF-7as the experimentalsubject to inspect the antitumor activity of the GO@Ag-DOX-NGR under NIR. Itturned out that the toxicity of GO and GO@Ag are very low without the irradiation ofNIR, however, the toxicity of them increased significantly due to the effect of photothermal therapy of the GO. After the linkage of DOX, the inhibition to MCF-7cells greatly enhanced and more red fluorescence (DOX signal) was observed in cellnucleus due to the presence of DOX after irradiated by NIR, indicating that NIR lightcan promote the release of GO@Ag-DOX-NGR in MCF-7cell significantly.In vivo, the S180tumor-bearing mice were chosen as the model to examine thetissue distribution and the tumor suppression of GO@Ag-DOX-NGR. Meanwhile, wealso investigated the X-ray imaging of GO@Ag-DOX-NGR in vivo. The resultsshowed that the distribution of DOX in tumor increased while decreased in heart andkidney under NIR. The drug system GO@Ag-DOX-NGR also had the characteristicsof X-ray imaging.To sum up, the drug delivery system GO@Ag-DOX-NGR is targeting and NIRsensitive. Besides, it has the function of X-ray imaging. The NIR-responsive drugdelivery may be promising for the in future cancer therapy.