Targeted Nanoactuator-Integrated Multicomponent Supramolecular Assemblies for Augmented Chemo/Chemodynamic Combination Therapies

Lung cancer remains the leading cause of cancer mortality, highlighting the need for innovative therapies. Aloe-emodin (AE), a natural anthraquinone from Aloe vera, faces clinical challenges due to tumor heterogeneity and immunosuppressive microenvironments. To address this, we combine chemodynamic therapy (CDT) with a novel supramolecular assembly (MIL-101(Fe)-Fc@AE@FACD), designed by functionalizing iron-based metal-organic frameworks (MIL-101(Fe)) with folic acid-conjugated cyclodextrin (FACD) for tumor targeting. This assembly enables dual therapeutic mechanisms: CDT-induced reactive oxygen species (ROS) generation and pH-triggered AE release. In vitro, it shows enhanced cytotoxicity against A549 cells, reducing cell viability to <15%. In vivo, it significantly inhibits tumor growth with minimal hepatorenal toxicity. This hybrid supramolecular platform enhances the antitumor efficacy of AE against lung cancer.