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.Keywords: chemotherapy; CT imaging; gold nanoparticles; hyaluronic acid targeting; laponite;

We report the synthesis, characterization and utilization of LAPONITE®-stabilized magnetic iron oxide nanoparticles (LAP-Fe3O4 NPs) as a high performance contrast agent for in vivo magnetic resonance (MR) detection of tumors. In this study, Fe3O4 NPs were synthesized by a facile controlled coprecipitation route in LAP solution, and the formed LAP-Fe3O4 NPs have great colloidal stability and about 2-fold increase of T2 relaxivity than Fe3O4 NPs (from 247.6 mM−1 s−1 to 475.9 mM−1 s−1). Moreover, cytotoxicity assay and cell morphology observation demonstrate that LAP-Fe3O4 NPs display good biocompatibility in the given Fe concentration range, and in vivo biodistribution results prove that NPs can be metabolized and cleared out of the body. Most importantly, LAP-Fe3O4 NPs can not only be used as a contrast agent for MR imaging of cancer cells in vitro due to the effective uptake by tumor cells, but also significantly enhance the contrast of a xenografted tumor model. Therefore, the developed LAP-based Fe3O4 NPs with good colloidal stability and exceptionally high transverse relaxivity may have tremendous potential in MR imaging applications.

In this study, multiwalled carbon nanotubes (MWCNTs) were used to encapsulate a model anticancer drug, doxorubicin (Dox). Then, the drug-loaded MWCNTs (Dox/MWCNTs) with an optimized drug encapsulation percentage were mixed with poly(lactide-co-glycolide) (PLGA) polymer solution for subsequent electrospinning to form drug-loaded composite nanofibrous mats. The structure, morphology, and mechanical properties of the formed electrospun Dox/PLGA, MWCNTs/PLGA, and Dox/MWCNTs/PLGA composite nanofibrous mats were characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and tensile testing. In vitro viability assay and SEM morphology observation of mouse fibroblast cells cultured onto the MWCNTs/PLGA fibrous scaffolds demonstrate that the developed MWCNTs/PLGA composite nanofibers are cytocompatible. The incorporation of Dox-loaded MWCNTs within the PLGA nanofibers is able to improve the mechanical durability and maintain the three-dimensional structure of the nanofibrous mats. More importantly, our results indicate that this double-container drug delivery system (both PLGA polymer and MWCNTs are drug carriers) is beneficial to avoid the burst release of the drug and able to release the antitumor drug Dox in a sustained manner for 42 days. The developed composite electrospun nanofibrous drug delivery system may be used as therapeutic scaffold materials for post-operative local chemotherapy.

In this study, we covalently conjugated polyethylene glycol-linked lactobionic acid (PEG-LA) onto the surface of laponite (LAP) nanodisks for the targeted delivery of doxorubicin (DOX) to liver cancer cells. LAP nanodisks were firstly modified with 3-aminopropyldimethylethoxysilane to introduce amino groups on the surface, and then PEG-LA were successfully conjugated to form targeted LM-PEG-LA nanodisks via EDC chemistry. Finally, the anticancer drug DOX was encapsulated into the synthesized nanocarriers with an exceptionally high loading efficiency of 91.5%. In vitro release studies showed that LM-PEG-LA/DOX could release drugs in a sustained manner with a higher speed under acidic conditions than that under physiological ones. MTT assay results proved that LM-PEG-LA/DOX displayed a significant higher therapeutic efficacy in inhibiting the growth of hepatocellular carcinoma cells (HepG2 cells) than untargeted ones at the same DOX concentration. The targeting specificity of LM-PEG-LA/DOX was further demonstrated by flow cytometric analysis and confocal laser scanning microscopy. The developed LA-modified LAP nanodisks could serve as a targeted carrier for efficient loading and specific delivery of different anticancer drugs to liver cancer cells.

We report the synthesis, characterization and utilization of LAPONITE®-stabilized magnetic iron oxide nanoparticles (LAP-Fe3O4 NPs) as a high performance contrast agent for in vivo magnetic resonance (MR) detection of tumors. In this study, Fe3O4 NPs were synthesized by a facile controlled coprecipitation route in LAP solution, and the formed LAP-Fe3O4 NPs have great colloidal stability and about 2-fold increase of T2 relaxivity than Fe3O4 NPs (from 247.6 mM−1 s−1 to 475.9 mM−1 s−1). Moreover, cytotoxicity assay and cell morphology observation demonstrate that LAP-Fe3O4 NPs display good biocompatibility in the given Fe concentration range, and in vivo biodistribution results prove that NPs can be metabolized and cleared out of the body. Most importantly, LAP-Fe3O4 NPs can not only be used as a contrast agent for MR imaging of cancer cells in vitro due to the effective uptake by tumor cells, but also significantly enhance the contrast of a xenografted tumor model. Therefore, the developed LAP-based Fe3O4 NPs with good colloidal stability and exceptionally high transverse relaxivity may have tremendous potential in MR imaging applications.