Pickering-Nanosheet Wrappers for Surfactant-Free Cancer Drug Delivery

Abstract The clinical efficacy of hydrophobic chemotherapeutics is frequently compromised by the systemic toxicity of synthetic surfactants and the instability of current drug formulations. While two-dimensional (2D) nanomaterials possess inherent geometrical advantages for interfacial stabilization, their potential as surfactant-free drug delivery vehicles remains underutilized. Here, we report a highly stable nanocarrier platform utilizing monolayer zirconium phosphate nanosheets as Pickering emulsifiers to encapsulate docetaxel. Unlike conventional formulations, these 2D nanosheets self-assemble at the interface to form a nanosheet-stabilized hybrid matrix, conferring exceptional colloidal stability without the need for toxic organic solvents as vehicles. In vitro studies demonstrate that these carriers are efficiently internalized by taxane-resistant ovarian cancer cells (SKOV3TR), resulting in potent, dose-dependent cytotoxicity. Furthermore, ex vivo assays reveal that these nanosheet-stabilized carriers eliminate the severe hemolysis associated with clinical vehicles (Tween 80/ethanol). These findings establish a foundational physical–chemical strategy for formulating surfactant-free Pickering nanocarriers.