Preparation And Functionalization Of Laponite?-Polyethylenimine-modified Gold And Anticancer Drug Nanoplatform For Theranostic Of Cancer Applications

In recent years,the development of theranostic nanoplatforms applied in the diagnosis and treatment of tumor has been a research highlight in the field of nanomedicine.Among a variety of nanocarriers,inorganic nanoparticles with the unique internal structure and excellent drug loading capacity have been widely studied in cancer therapy,but the difficulty of surface modification and poor stability limit their further application in biomedical field.Therefore,the conjugation of polymer on the surface of inorganic nanoparticles may build hybrid nanoparticles with improved stability and easy to modifiy targeting or imaging agents,which may be promising theranostic nanoplatforms for cancer imaging and chemotherapy.In this study,laponite(LAP)nanodisks and polyethylenimine(PEI)were used to build a hybrid theranostic nanoplatform for targeted computed tomography(CT)imaging and chemotherapy of cancer cells overexpressing CD44 receptors.Firstly,amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol)(PLA-PEG-COOH)were assembled on the surface of LAP nanodisksvia hydrophobic interaction,and then PEI were conjugated by the formation of amide groups via1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC)coupling chemistry.The developed LAP-PLA-PEG-PEI nanoparticles were used as templates for the embedding of gold nanoparticles(Au NPs),followed by modification with hyaluronic acid(HA)as a targeting ligand for cancer cells overexpressing CD44 receptors.Finally,anticancer drug doxorubicin(DOX)was loaded.The formed LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX nanocomplexes display good stability,a high drug loading efficiency as 91.0 ± 1.8%,and sustained drug release profile with a p H-sensitive manner.In vitro cell viability assay,flow cytometric analysis and laser scanning confocal microscopy observation demonstrate that the formed nanocomplexes can specifically deliver and inhibit cancer cells overexpressing CD44 receptors.In vivo experiments illustrate that LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX nanocomplexes can not only significantly inhibit the growth of tumors and decrease the side-effect of DOX,but also be used as a targeted contrast agent for CT imaging of tumors.Therefore,the developed LAP-PLA-PEG-PEI-(Au~0)50-HA/DOX nanocomplexes can be used as a promising theranostic platform for targeted imaging and chemotherapy of CD44-overexpressed tumors.