Preparation Of Light Responsive Size Variable Drug Delivery Systems Based On Gold Nanoparticles And Study On Their Biological Activity

Cancer is one of the main causes of death in the world.At present,nano-drug carriers have become powerful tools against cancer,which could reach tumor site by enhanced permeability and retention（EPR）effects（100-200 nm）or surface conjugate targeted molecules.However,nano-drug carriers are difficult to penetrate the deep of tumor,due to the poor vascular function,high interstitial fluid pressure and dense extracellular matrix in tumor tissue,which is the main reason for the recurrence of the tumor.In this study,based on the above research background,the gold nanoparticles were developed and applied to the field of deep tumor therapy.We synthesized multifunctional nano-drug carriers with structural variable,which solved the key problem of tumor penetration.The main contents include the following two aspects:Based on a liposomes（lip）encapsulated oleanolic acid（OA）,which were modified gold nanoflowers（OL@GNFs）.After NIR irradiation,the structure and size of the drug delivery system will change.The OL@GNFs exhibited uniform morphology,excellent biocompatibility and photothermal conversion efficiency.Moreover,under NIR laser irradiation,the heating effect induced by OL@GNFs can not only trigger photothermal therapy（PTT）to kill cancer cells directly,but also release chemotherapy drugs.The OL@GNFs can achieve a good therapeutic effect,and cell survival rate is only 27%.At the same time,porphyrin,a photosensitizer,was loaded in the drug carriers（COL@GNFs）,which realized photodynamic therapy.The combined effect of multiple treatment methods made the survival rate of tumor cells only 17%.The results of in vivo experiments showed that the relative tumor volume of the COL@GNFs group（V/V₀,0.65±0.43）was significantly lower than that of the PBS group（21.2±0.38）,suggesting excellent tumor therapy efficiency.Furthermore,a novel structure-tunable nanomedicine（PDA@GNRs-DOX/Ce6）was designed,doxorubicin（DOX）modified gold nanorods（GNRs）and chlorin e6（Ce6）were loaded simultaneously onto the surface of polydopamine（PDA）sphere.The PDA@GNRs-DOX/Ce6 exhibited uniform morphology,excellent biocompatibility and photothermal conversion efficiency.The nano-drug carriers improve the tumor therapy process:firstly,the primary drug carriers were accumulated on tumor surface via enhanced permeability and retention effect,and then the secondary structures penetrate into tumor deeply to damage the tumor stem cells after the primary structures were disintegrated into small particles under NIR laser irradiation.PDA@GNRs-DOX/Ce6 were disintegrated into GNRs and DOX within 15 min with the resultant drug release.In addition,drug release of PDA@GNRs-DOX/Ce6 was measured with NIR on-off switch,and the result showed its drug release was NIR-dependent and low pH favorable.The relative tumor volume（V/V₀,0.47±0.31）in PDA@GNRs-DOX/Ce6 group was lower significantly than that of the PBS control（26.5±0.98）,suggesting excellent tumor therapy efficiency.Therefore,this nanodrug platform was expected to be a potential tumor therapy agent due to both superior drug delivery and high tumor therapy efficiency.