Citation: Daniele,V.; Volpe, A.R.; Cesare, P.; Taglieri, G. MgO Nanoparticles Obtained from an Innovative and Sustainable Route and Their Applications in Cancer Therapy. Nanomaterials 2023, 13, 2975. https://doi.org/10.3390/ nano13222975 Academic Editor: Alexander Gusev Received: 11 October 2023 Revised: 13 November 2023 Accepted: 17 November 2023 Published: 19 November 2023 Copyright: © 2023 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 (https:// creativecommons.org/licenses/by/ 4.0/). nanomaterials Article MgO Nanoparticles Obtained from an Innovative and Sustainable Route and Their Applications in Cancer Therapy Valeria Daniele 1, * , Anna Rita Volpe 2 , Patrizia Cesare 2 and Giuliana Taglieri 1, * 1 Department of Industrial and Information Engineering and Economics, University of L’Aquila, Piazzale E. Pontieri 1, Monteluco di Roio, Roio Poggio, 67100 L’Aquila, Italy 2 Department of Life, Health and Environmental Sciences, University of L’Aquila, Edificio Renato Ricamo, Via Vetoio, Coppito, 67100 L’Aquila, Italy; annarita.volpe@univaq.it (A.R.V.); patrizia.cesare@univaq.it (P.C.) * Correspondence: valeria.daniele@univaq.it (V.D.); giuliana.taglieri@univaq.it (G.T.); Tel.: +39-862-434205 (V.D.); +39-862-434234 (G.T.) Abstract: This paper aimed to evaluate the biological damages towards diseased cells caused by the use of MgO nanoparticles (NPs). The NPs are produced by a calcination process of a precursor, which is an aqueous suspension of nanostructured Mg(OH) 2 , in turn synthesized following our original, time-energy saving and scalable method able to guarantee short times, high yield of production (up to almost 10 kg/week of NPs), low environmental impact and low energy demand. The MgO NPs, in the form of dry powders, are organized as a network of intercrystallite channels, in turn constituted by monodispersed and roughly spherical NPs < 10 nm, preserving the original pseudo hexagonal-platelet morphology of the precursor. The produced MgO powders are diluted in a PBS solution to obtain different MgO suspension concentrations that are subsequently put in contact, for 3 days, with melanoma and healthy cells. The viable count, made at 24, 48 and 72 h from the beginning of the test, reveals a good cytotoxic activity of the NPs, already at low MgO concentrations. This is particularly marked after 72 h, showing a clear reduction in cellular proliferation in a MgO- concentration-dependent manner. Finally, the results obtained on human skin fibroblasts revealed that the use MgO NPs did not alter at all both the vitality and proliferation of healthy cells. Keywords: MgO nanoparticles; scalable and time-energy synthesis; ion exchange process; XRD; HRTEM; therapeutic applications; MgO against cancer growth; growth curves of melanoma cells 1. Introduction One of the major diseases currently afflicting the population worldwide is cancer, in which a group of cells reveal an uncontrolled growth into the body that leads, sometimes, to the formation of metastasis [1,2]. The conventional approaches used to treat cancer are chemotherapy, radiation and surgery; nevertheless, these procedures often present severe limitations since they can affect both diseased and healthy cells in the body. So, the possibility of employing metal oxide nanoparticles (NPs) in place of harmful techniques has become the current intriguing challenge, allowing for the establishment of a new criterion for the development of NPs in the medical field, where extensive applications are required [14]. This is due to the anticancer activity of the NPs depending on their intrinsic features such as antioxidant action, as well as to their ability to interact with proteins, nucleic acids and lipids, both inside and outside the cell. In particular, the potential cytotoxicity of NPs against cancer cells is related to oxidative stress stimulated by reactive oxygen species (ROS), leading to an apoptotic process and inducing significant cell structure damage to membrane lipids, membrane proteins and to the nuclear membrane [2,3,511]. Metal oxide NPs are also able to produce free radicals that kill cancer cells if stimulated by an external radiation source, such as hyperthermia, in response to the application of infrared rays or magnetic fields. In particular, the NPs acting as co-adjuvant agents Nanomaterials 2023, 13, 2975. https://doi.org/10.3390/nano13222975 https://www.mdpi.com/journal/nanomaterials