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

Caccamo, D., Currò, M., Lentile, R., Verderio, E.A. ORCID: 0000-0001-9153-8997, Scala, A., Mazzaglia, A., Pennisi, R., Musarra-Pizzo, M., Zagami, R., Neri, G., Rosmini, C., Potara, M., Focsan, M., Astilean, S., Piperno, A. and Sciortino, M.T., 2020. Intracellular fate and impact on gene expression of doxorubicin/cyclodextrin-graphene nanomaterials at sub-toxic concentration. International Journal of Molecular Sciences, 21 (14): 4891. ISSN 1661-6596

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Abstract

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.

Item Type: Journal article
Publication Title: International Journal of Molecular Sciences
Creators: Caccamo, D., Currò, M., Lentile, R., Verderio, E.A., Scala, A., Mazzaglia, A., Pennisi, R., Musarra-Pizzo, M., Zagami, R., Neri, G., Rosmini, C., Potara, M., Focsan, M., Astilean, S., Piperno, A. and Sciortino, M.T.
Publisher: MDPI AG
Date: 10 July 2020
Volume: 21
Number: 14
ISSN: 1661-6596
Identifiers:
NumberType
10.3390/ijms21144891DOI
1359667Other
Rights: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license http://creativecommons.org/licenses/by/4.0/).
Divisions: Schools > School of Science and Technology
Record created by: Linda Sullivan
Date Added: 28 Sep 2020 07:53
Last Modified: 28 Sep 2020 07:53
URI: http://irep.ntu.ac.uk/id/eprint/40967

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