https://biointerfaceresearch.com/ 1 of 14 Article Volume 13, Issue 1, 2023, 60 https://doi.org/10.33263/BRIAC131.060 Magnetic ZnO/CdO Nanocomposite for Effective Drug Delivery System for Cancer Therapy Hanan H. Mohamed 1,* , Tamer E. Youssef 2 , Doaa Abdel Fadeel 3 1 Chemistry Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, 11795, Egypt; m_h_hanan_0503@yahoo.com (H.H.M.); 2 Applied Organic Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt; Tamezzat@yahoo.com (T.E.Y.); 3 Pharmaceutical Technology Unit, Department of Medical Applications of Laser, National Institute of Laser Enhanced Sciences, Cairo University, Giza, Egypt; doaa.fadeel@niles.edu.eg (D.A.F.); * Correspondence: m_h_hanan_0503@yahoo.com (H.H.M.); Scopus Author ID 55172120500 Received: 20.11.2021; Accepted: 19.12.2021; Published: 30.01.2022 Abstract: ZnO, ZnO/CdO, and Magnetic Ni-ZnO/CdO nanocomposite have been eco-friendly synthesized using Black Rice Husk Extract (BRHE) and water instead of hazardous chemicals and solvents. The anticancer drug Doxorubicin (Dox) was loaded on the PVA-coated biomimetic nanomaterials. The successful synthesis of the pure nanomaterials and the Dox-nanomaterial systems has been confirmed by evaluating their structural, crystalline, textural, surface, and optical properties using various characterization techniques. The Dox-nanomaterials systems were used as anticancer drugs against HEPG2 cells as a model of human cancerous cells. The in vitro Dox release was slower and more sustained from Ni-ZnO/CdO composite compared to the other individual nanomaterials, suggesting that a hydrogen bond strongly attached more Dox molecules to the surface Ni-ZnO/CdO. Moreover, the cytotoxicity investigations on the HEPG2 cell line showed that higher toxicity was obtained by Ni-doped nanocomposite, consistent with the results of in vitro release. This study provides novel magnetic Nanocarriers that can be used as anticancer drug delivery systems after more in vivo investigations on animals or clinical investigations. Keywords: magnetic Ni- ZnO/CdO; green synthesis; doxorubicin; anticancer drug delivery; HEPG2 cell. © 2022 by the authors. 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/). 1. Introduction Semiconductor metal oxide nanoparticles attracted great attention in biomedical applications such as drug delivery, cancer therapy, and technological applications such as optical and nanoelectronic devices and photocatalysis [1, 2]. It has been found that metal oxide nanoparticles can kill cancer cells in low concentrations. Zinc oxide (ZnO) nanoparticles have potential in cancer therapy due to their ability to induce cancer cell apoptosis [3]. In addition, cadmium oxide (CdO) nanoparticles were found to be an efficient metal oxide nanomaterial for cancer therapy via destruction of the cancer cell wall and the interaction with DNA causing protein damage [4]. Interestingly, CdO nanoparticles were found to be not dangerous for human and mammalian cells. CdO coupled ZnO with well-defined morphology may enhance the anticancer activity in a better way.