Micelle-assisted synthesis of spherical MIL-100(Fe) nanoparticles for pH-responsive camptothecin delivery and chemodynamic cancer therapy.

Nano-metal-organic frameworks (nMOFs) have been widely investigated as drug carriers owing to their high surface area, tunable porosity, and ordered structure. However, conventional hydrothermal and solvothermal synthesis routes often yield irregular morphologies, broad size distributions, and limited colloidal stability, restricting cellular uptake, biodistribution, and therapeutic efficacy. Here, we report a micelle-assisted synthesis strategy using surfactant modulators to regulate nucleation and crystal growth of MIL-100(Fe) nanoparticles. The resulting uniform, quasi-spherical nanoparticles exhibited high drug-loading capacity and pH-responsive drug release. Furthermore, MIL-100(Fe) generated reactive oxygen species (ROS) through Fenton-mediated reactions, enabling chemodynamic therapy. The in vitro studies using L929, HeLa, MCF-7, MDA-MB-231, and A549 cells demonstrated time- and dose-dependent, cell-type-specific cytotoxicity. Enhanced internalisation in malignant cells increased intracellular ROS, inducing apoptotic cell death and synergistic CPT-based chemotherapy. Overall, this study establishes a structure-property-biological response correlation, demonstrating that controlled nanoparticle morphology can modulate biological responses, thereby improving therapeutic efficacy against cancer.