▎ 摘　　要

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(R)DOX, tracked by FLIM, Raman mapping and fluorescence microscopy, evidenced the efficient cellular uptake of GCD(R)DOX and the presence of DOX in the nucleus, without graphene carrier. The NanoString nCounter (TM) platform provided evidence for 34 (out of 700) differentially expressed cancer-related genes in HEp-2 cells treated with GCD(R)DOX (25 mu g/mL) compared with untreated cells. Cells treated with GCD alone (25 mu g/mL) showed modification for 16 genes. Overall, 14 common genes were differentially expressed in both GCD and GCD(R)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(R) technology, such as sensibility and the direct RNA measurements, could be the cornerstone in this field.