Metal-Based Nanomaterials as Delivery Systems for Dihydroartemisinin in Anticancer Therapy: A Systematic Review

Dihydroartemisinin (DHA), the principal active metabolite of artemisinin and an established component of first-line antimalarial therapy, shows broad anticancer activity in preclinical models. Its translation into oncology is nonetheless constrained by poor aqueous solubility, a short plasma half-life, rapid clearance, and low bioavailability. Loading DHA into metal-based nanomaterials has been proposed as a way to overcome these pharmacokinetic limitations while simultaneously exploiting the intrinsic redox reactivity of the metal centres for therapeutic benefit, since metals such as iron and manganese can catalyse Fenton or Fenton-like reactions that amplify oxidative stress. Despite growing interest in this design strategy, no systematic synthesis has appraised the evidence for DHA conjugated to or encapsulated within metal-based nanomaterials. This systematic review addresses that gap. It synthesises the types, physicochemical characteristics, anticancer mechanisms, and comparative efficacy of metal-based nanomaterial systems carrying DHA relative to free DHA, drawing on preclinical in vitro and in vivo evidence. The review is reported in accordance with the PRISMA 2020 statement, and findings are combined through a structured narrative synthesis following the Synthesis Without Meta-analysis (SWiM) guideline. This registration deposits a timestamped, publicly accessible record of the methodology as applied.