The theranostic ability of a new fluorescently labeled cationic cyclodextrin−graphene nanoplatform (GCD@Ada-Rhod) was investigated by studying its intracellular trafficking and its ability to deliver plasmid DNA and microRNA . CD units grafted on G surfaces fulfill different roles: (i) they provide unique biological features to G, improving its biocompatibility and colloidal stability; (ii) CD cavities are recognition sites for the
entrapment of small hydrophobic compounds; and (iii) cationic external CD rims (substituted with quaternary amino groups) can interact with oligonucleotides by electrostatic interactions. Taking advantage of the high affinity of CD cavities for an adamantane unit (K ≈ 105 M−1), the adamantane-modified rhodamine (Ada-Rhod) was synthesized and used to obtain a platform (GCD@Ada-Rhod) that has the potential to become theranostic.
The biological results evidenced an unforeseen caveolae-mediated endocytosis internalization pathway (generally expected for particles <200 nm), despite the fact that the GCD@Ada-Rhod size is about 400 nm (by DLS and TEM data). We supposed that the internalization pathway was driven by physical−chemical features of GCD@Ada-Rhod, and the caveolae-mediated uptake enhanced the transfection efficiency, avoiding the lysosomal acid degradation.
Studying the cellular effects of internalized miRNA-15a on the oncogene protein BCL-2 at two different concentrations (N/P = 10 and 5) the level of the anti-apoptotic protein BCL-2 was found to be tuned by the N/P ratio. High levels of delivered miRNA-15a (i.e., N/P = 5) induced an up-regulation of BCL-2, whereas a reduction of the BCL-2 level was detected at N/P = 10, suggesting that the low amount of delivered miRNA-15a is able to down-regulate BCL-2.
 Anna Piperno, Antonino Mazzaglia, Angela Scala, Rosamaria Pennisi, Roberto Zagami, Giulia Neri, Serena M. Torcasio, Consolato Rosmini, Placido G. Mineo, Monica Potara, Monica Focsan, Simion Astilean, Grace Guoying Zhou, Maria Teresa Sciortino
Casting Light on Intracellular Tracking of a New Functional Graphene-Based MicroRNA Delivery System by FLIM and Raman Imaging.
ACS Appl. Mater. Interfaces 2019, 11, 49, 46101-46111. https://pubs.acs.org/doi/10.1021/acsami.9b15826