Synthesis and Characterization of Arsenic(III) Oxide Nanoparticles as Potent Inhibitors of MCF 7 Cell Proliferation through Proapoptotic Mechanism Biswajit Das 1 & Hasimur Rahaman 2 & Sujit Kumar Ghosh 2 & Mahuya Sengupta 1 # Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Recent advances in the nanosciences have revolutionized the diagnosis and treatment of diseases like cancers. Arsenic(III) trioxide, best known as a toxic agent, is routinely used in treating different types of leukemia. Besides its application as a chemotherapeutic drug for treating acute promyelocytic leukemia, several attempts have been made to use arsenic trioxide (ATO) against solid tumors. This is however, restricted because of the rapid renal clearance and dose-associated side effects of ATO. This work aims to address these limitations of ATO in chemotherapy by synthesizing biocompatible human serum albumin coated arsenic trioxide nanoparticles (HSA-ATONPs) by an alkaline hydrothermal process, taking sodium arsenate as a precur- sor. Compared with bulk ATO, these are found to have better cytotoxicity as indicated by an in vitro study with the cancer cell line MCF7. As envisaged by transmission electron microscopy, canonical signs of apoptosis were observed in the MCF 7 cells treated with HSA-ATONPs, confirmed by Annexin V-FITC staining. The study thus, reports an augmentation of the chemotherapeutic potential of arsenic trioxide in its nanoparticulate form with its surface functionalization of human serum albumin. Keywords Arsenic trioxide . Nanoparticles . Cytotoxicity . Apoptosis . MCF7 cells 1 Introduction Arsenic is used as a chemotherapeutic agent in leukemia [1] and is one of the most commonly used ingredients in complementary and alternative medicine as a treatment for a variety of ailments and diseases [2–5]. In modern medicine, FDA-approved drugs namely TRISENOX® and ARSENOX- containing arsenic trioxide (As 2 O 3 or ATO) are well-known anticancer drugs for treatments of refractory acute promyelocytic leukemia (APL) and relapsed/refractory multi- ple myeloma including adult T cell leukemia and lymphoma [6–9]. In China, ATO has been approved for palliative treat- ment of patients with unresectable hepatocellular carcinoma (HCC) as a single agent for chemotherapy or in combination with transarterial chemoembolization (TACE) therapy in he- patocellular carcinoma [10]. ATO reduces migration and in- vasion of cancer cells and is also known to induce apoptosis of cervical, ovarian, and prostate cancer cells in vitro [11, 12]. Although limited, there has been reports of the clinical use of ATO against acute promyelocytic leukemia and chronic mye- logenous leukemia (CML). The inherent toxicity of arsenic is the major cause for the limited use of arsenic in leukemia chemotherapy. Moreover, as compared with leukemia, little efficacy of ATO has been observed in the treatment of solid tumors [7, 13]. This is due to its inherent toxicity that include peripheral neuropathies and liver failure [14] in addition to rapid renal clearance, limiting its uptake in tumors [15]. Thus, attempts have been made to overcome these toxic Highlights • Synthesis of albumin-coated As 2 O 3 nanoparticles (HSA-ATONPs) • Uptake and intracellular localization of the HSA-ATONPs in MCF7 cells • Apoptosis of MCF7 cells by HSA-ATONPs at a lower dose compared to bulk ATO * Mahuya Sengupta senguptamahuya35@gmail.com Biswajit Das biswajit.das@bioinfoaus.ac.in Hasimur Rahaman hasichem@gmail.com Sujit Kumar Ghosh sujit.kumar.ghosh@aus.ac.in 1 Department of Biotechnology, Assam University, Silchar, Assam 788011, India 2 Department of Chemistry, Assam University, Silchar, Assam 788011, India BioNanoScience https://doi.org/10.1007/s12668-020-00726-0