Nanomaterials 2021, 11, 2628. https://doi.org/10.3390/nano11102628 www.mdpi.com/journal/nanomaterials Article Iron‐Doped ZnO Nanoparticles as Multifunctional Nanoplatforms for Theranostics Marco Carofiglio, Marco Laurenti, Veronica Vighetto, Luisa Racca, Sugata Barui, Nadia Garino, Roberto Gerbaldo, Francesco Laviano and Valentina Cauda * Department of Applied Science and Technology, Politecnico di Torino, C.so Duca degli Abruzzi 24, 10129 Turin, Italy; marco.carofiglio@polito.it (M.C.); marco.laurenti@polito.it (M.L.); veronica.vighetto@polito.it (V.V.); luisa.racca@polito.it (L.R.); sugata.barui@polito.it (S.B.); nadia.garino@polito.it (N.G.); roberto.gerbaldo@polito.it (R.G.); francesco.laviano@polito.it (F.L.) * Correspondence: valentina.cauda@polito.it; Tel.: +39‐011‐090‐7389 Abstract: Zinc oxide nanoparticles (ZnO NPs) are currently among the most promising nanomaterials for theranostics. However, they suffer from some drawbacks that could prevent their application in nanomedicine as theranostic agents. The doping of ZnO NPs can be effectively exploited to enhance the already‐existing ZnO properties and introduce completely new functionalities in the doped material. Herein, we propose a novel synthetic approach for iron‐doped ZnO (Fe:ZnO) NPs as a multifunctional theranostic nanoplatform aimed at cancer cell treatment. Pure ZnO and Fe:ZnO NPs, with two different levels of iron doping, were synthesized by a rapid wet‐chemical method and analyzed in terms of morphology, crystal structure and chemical composition. Interestingly, Fe:ZnO NPs featured bioimaging potentialities thanks to superior optical properties and novel magnetic responsiveness. Moreover, iron doping provides a way to enhance the electromechanical behavior of the NPs, which are then expected to show enhanced therapeutic functionalities. Finally, the intrinsic therapeutic potentialities of the NPs were tested in terms of cytotoxicity and cellular uptake with both healthy B lymphocytes and cancerous Burkitt’s lymphoma cells. Furthermore, their biocompatibility was tested with a pancreatic ductal adenocarcinoma cell line (BxPC‐3), where the novel properties of the proposed iron‐doped ZnO NPs can be potentially exploited for theranostics. Keywords: ZnO; iron doping; piezoelectricity; magnetic NPs; theranostics; cancer treatment 1. Introduction Novel therapeutic approaches based on the use of smart nanomaterials are considered the frontiers in the development of next‐generation, multifunctional nanosystems aiming for nanomedicine applications. Examples include theranostic nanoparticles (NPs), i.e., nanosystems capable of combining therapeutic and diagnostic functionalities to deliver and activate a therapeutic agent in a specific position inside the body and to report the status of the disease and/or the localization of the therapeutic agent at the same time [1]. One of the main and most appealing applications of theranostics is surely in the field of antitumoral treatments [2]. Indeed, the possibility to exploit both imaging capabilities and a therapeutic action of the theranostic agent in the human body, as well as to guide it toward the specific site of interest, gathers relevant advantages in terms of personalized medicine, allowing the application of a customized therapy and real‐time diagnosis solely for the targeted organ or tissue. In this regard, the study of theranostic nanoparticles gained relevant attention. Thanks to the reduced size, NPs represent one of the most suitable systems compatible with the cellular dimensions. This aspect is also efficiently combined with their superior Citation: Carofiglio, M.; Laurenti, M.; Vighetto, V.; Racca, L.; Barui, S.; Garino, N.; Gerbaldo, R.; Laviano, F.; Cauda, V. Iron‐Doped ZnO Nanoparticles as Multifunctional Nanoplatforms for Theranostics. Nanomaterials 2021, 11, 2628. https:// doi.org/10.3390/nano11102628 Academic Editor: Pablo Botella Received: 9 September 2021 Accepted: 1 October 2021 Published: 6 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 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/).