LAPONITE-Polyethylenimine Based Theranostic Nanoplatform for Tumor-Targeting CT Imaging and Chemotherapy.

Abstract

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. First, amphiphilic copolymer poly(lactic acid)-poly(ethylene glycol) (PLA-PEG-COOH) were assembled on the surface of LAP nanodisks via hydrophobic interaction, and then PEI were conjugated by the formation of amide groups via1-ethyl-3-(3-(dimethylamino)propyl) 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-(Au0)50-HA/DOX nanocomplexes display good stability, a high drug loading efficiency as 91.0 ± 1.8%, and sustained drug release profile with a pH-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-(Au0)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-(Au0)50-HA/DOX nanocomplexes can be used as a promising theranostic platform for targeted imaging and chemotherapy of CD44-overexpressed tumors.