Preparation And Biological Activity Study Of Dual-drugs Loaded Nanoparticles For Intelligent Delivery And Synergistic Therapy

Cancer is one of the major public health problems in the world with high morbidity and high mortality.Therefore,the prevention and treatment of cancer has attracted much attention.At present,the more widely used and clinically applied therapeutic methods are chemotherapy based on platinum drugs.Although many achievements have been made in the research and development,platinum drugs are limited in clinical because of its lack of the specific recognition of tumor cells and drug resistance.Targeted therapy and synergistic therapy of tumors have gradually become a research focus in in recent years.In this study,the nanoscale drug delivery systems(NDDSs)with targeting transport and controlled release were designed and prepared.We studied the delivery efficiency in vitro and synergistic therapeutic effect of NDDSs through biological experiments.In this study,we prepared CC-Pt@FA-Lipo which was modified with folate and loaded various drugs by the thin film hydration method.CC is an abbreviation for a conjugate of benzothiazole derivative and cholesterol.CC-Pt@FA-Lipo had a desirable particle size and good dispersibility,and its selectivity of tumor cells was enhanced due to the modification of folate.The photothermal conversion effect of ICG played a role of switch of controlled release and thermotherapy for tumor cells.In the investigation in vitro,CC-Pt@FA-Lipo showed excellent inhibition of cell proliferation on gastric cancer cell MGC-803 and breast cancer cell MDA-MB-231,and the inhibitory effect on MDA-MB-231 was even more significant.As novel anti-tumor methods,photodynamic therapy(PDT)and photothermal therapy(PTT)have attracted more attention recently.In this paper,a thermosensitive nanoparticle,cRGD/FA@CICNPs,was designed to realize the intelligent drug release and the combination of chemotherapy,PDT and PTT.The cisplatin and photosensitizers were co-delivered to tumor cells under the dual targeting strategy.The intracellular reactive oxygen species(ROS)produced by photodynamic therapy can effectively damage DNA,proteins,and membrane lipids,thereby promoting the apoptosis of tumor cells.We investigated the effects of concentration and time on the generation of intracellular ROS in MCF-7 cells,and conducted the quantitative and qualitative analyses by flow cytometry and confocal laser scanning microscope.The dual-targeting strategy can effectively increase the uptake efficiency of cRGD/FA@CICNPs in tumor cells and enhance the synergistic antitumor activity of MCF-7 cells and SGC-7901 cells.