Trifunctional polymer nanobeads are prepared by destabilization of a mixture of magnetic nanoparticles, quantum dots, and an amphiphilic polymer, followed by functionalization of the bead surface with folic acid molecules. The distribution of the nanoparticles within the nanobeads can be tuned using either acetonitrile or water as destabilizing solvent. The luminescence of the resulting beads can be tuned by varying the ratio of quantum dots per magnetic nanoparticles. The application of an external magnetic field (such as a small static magnet of 0.3 T) to the magnetic-fluorescent nanobeads allows the quantitative accumulation of the beads within a few hours depending on the total size of the beads. Furthermore, specific targeting of cancer cells overexpressing folate receptors is achieved thanks to the folic acid decorating the surface of the as-synthesized nanobeads. Folate receptor mediated cellular uptake of the folic acid-functionalized nanobeads is proven via both confocal imaging and transmission electron microscopy characterization. Cell sorting experiments performed with trifunctional nanobeads show quantitative recovering of targeted cells even when they are present at low percentage (up to 1%).
Poly(maleic anhydride-alt-1-octadecene), a cheap and commercially available polymer, was used to water-solubilize colloidal nanocrystals with various compositions, morphologies, and sizes. Highly pure nanoparticles with homogeneous distributions of sizes and surface charges were obtained after a single purification step of the polymer-coated particles by ultracentrifugation, saving precious time as compared to a previously published and similar polymer coating procedure. This simple strategy proved also to be generally applicable and represents a valid methodology to water-solubilize nanoparticles.
Hepatocellular carcinoma (HCC) accounts for over 80% of liver cancer cases and is highly malignant, recurrent, drug-resistant, and often diagnosed in the advanced stage. It is clear that early diagnosis and a better understanding of molecular mechanisms contributing to HCC progression is clinically urgent. Metabolic alterations clearly characterize HCC tumors. Numerous clinical parameters currently used to assess liver functions reflect changes in both enzyme activity and metabolites. Indeed, differences in glucose and acetate utilization are used as a valid clinical tool for stratifying patients with HCC. Moreover, increased serum lactate can distinguish HCC from normal subjects, and serum lactate dehydrogenase is used as a prognostic indicator for HCC patients under therapy. Currently, the emerging field of metabolomics that allows metabolite analysis in biological fluids is a powerful method for discovering new biomarkers. Several metabolic targets have been identified by metabolomics approaches, and these could be used as biomarkers in HCC. Moreover, the integration of different omics approaches could provide useful information on the metabolic pathways at the systems level. In this review, we provided an overview of the metabolic characteristics of HCC considering also the reciprocal influences between the metabolism of cancer cells and their microenvironment. Moreover, we also highlighted the interaction between hepatic metabolite production and their serum revelations through metabolomics researches.
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