Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration

The graphene road in nanomedicine still seems very long and winding because the current knowledge about graphene/cell interactions and the safety issues are not yet sufficiently clarified. Specifically, the impact of graphene exposure on gene expression is a largely unexplored concern. Herein, we investigated the intracellular fate of graphene (G) decorated with cyclodextrins (CD) and loaded with doxorubicin (DOX) and the modulation of genes involved in cancer-associated canonical pathways. Intracellular fate of GCD@DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD@DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter™ platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD@DOX (25 µg/mL) compared with untreated cells. Cells treated with GCD alone (25 µg/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD@DOX treated cells and 4 of these genes with an opposite trend. The modification of cancer related genes also at sub-cytotoxic G concentration should be taken in consideration for the rational design of safe and effective G-based drug/gene delivery systems. The reliable advantages provided by NanoString® technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field

Assembly of Polymers/Metal Nanoparticles and their Applications as Medical Devices

Metallic nanoparticles have attracted much attention and have found applications in diff erent fi elds such as medicine, pharmacy, controlled drug delivery, optics, electronics, and other areas. Among the most promising nanomaterials with antibacterial and antiviral properties are metallic nanoparticles (silver, gold, platinum, etc), which exhibit increased chemical activity due to their large surface to volume ratios, crystallographic surface structure and unique size-dependent optical, electrical and magnetic properties. However, it has been reported that bare metallic nanoparticles can be toxic. Th is supports the concept that this toxicity is associated to the presence of the bare metallic nanoparticle surface, while particles protected by an organic layer, i.e. polymer, are much more biocompatible, and thereby less toxic. Unrelated to the bare metallic surface, several recent studies indicate that, at a cellular level, metal nanoparticles interact with biological molecules within mammalian cells and can interfere with the antioxidant defense mechanism leading to the generation of reactive oxygen species (ROS). Increase of ROS levels may result in significant damage to cell structures known as oxidative stress. This review article reports on obtaining metallic nanoparticles with special emphasis on obtaining silver nanoparticles, their incorporation within various polymer materials, physiochemical and biological properties of such obtained systems as well as about their application as medical devices