Nanoscaffold-based 3D human liver spheroids for predictive hepatotoxicity screening of antimalarial compounds from the global health priority box

This study demonstrates the translational application of a validated nanoscaffold-based 3D human liver spheroid model for antimalarial drug in vitro hepatotoxicity assessment. By establishing a reference framework from clinically approved antimalarials and applying it to candidate compounds from the MMV GHPB, our platform enabled early classification of hepatotoxicity risk using a human-relevant, non-animal method. The findings support the integration of advanced 3D in vitro systems into antimalarial drug discovery pipelines to improve safety prediction, reduce reliance on animal testing, and accelerate the development of safer, more effective antimalarial therapies.