Nanoencapsulation of ferrocene incorporated thiourea and doxorubicin for treatment of acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the accumulation of undifferentiated myeloid precursors in the bone marrow and peripheral blood. Doxorubicin (DOX) is a frontline chemotherapeutic agent that exhibits potent antitumor activity but is hindered by cardiotoxicity, nephrotoxicity, poor solubility, and non-selective distribution. Ferrocene-incorporated thiourea (FITU) has demonstrated anticancer potential but remains limited by hydrophobicity and delivery challenges. The aim of this study was to investigate the therapeutic efficacy of FITU, DOX, and their combination by delivering them through polyethylene glycol (PEG)-coated liposomal nanoparticles. Nanoparticles for doxorubicin (DOX-Nps), Ferrocene incorporated thiourea (FITU), and their combination (FITU + DOX-Nps) were prepared via thin-film hydration and their particle size, surface charge, encapsulation efficiency, and in vitro drug release were characterized. The hemocompatibility, antioxidant activity, and cytotoxicity of the formulations were assessed via standard in vitro assays. In-vivo therapeutic efficacy was evaluated in Wistar rats with benzene-induced AML. Hematological parameters, organ function markers, survival rates, and histopathological analyses of the liver, kidney, and heart were performed. Statistical significance was determined via one-way ANOVA. The nanoparticle formulations presented an appropriate size distribution, high encapsulation efficiency, and sustained drug release profiles. Compared to free drugs liposomal formulations demonstrated improved biocompatibility, reduced hemolysis, and enhanced antioxidant and cytotoxic effects, in vitro. In vivo, animals treated with FITU + DOX Nps presented significant restoration of hematological parameters and organ function, improved survival rates and reduced leukemic infiltration in histological assessments. The PEG coated liposomes extended systemic circulation and improved overall therapeutic outcomes. Co delivery of FITU and DOX via PEG coated liposomal nanoparticles is a promising strategy for enhancing therapeutic efficacy and minimizing systemic toxicity in AML. These findings support further preclinical development of this nano-formulation as a targeted treatment modality for leukemia. • Liposomal nanoparticles were made from FITU, DOX, or a combination of both. • Compared with free drugs liposomes have better efficacy and less toxicity. • Nanoparticle delivery improves AML treatment outcomes.