Soft Magnetism Meets Self-Assembly: Molecularly Engineered Magnetic Ionic Liquid Nanomicelles for the Solubilization, Sustained Release, and Anticancer Activity of Quercetin.

The development of IL-N8 and its magnetic micelle-forming derivative MIL-N8 offers a promising advancement in nanostructured carriers for efficient hydrophobic drug delivery. The structural validation for MIL-N8 was obtained through Raman, EPR, and NMR spectroscopy, which suggested successful synthesis and molecular integrity of both IL-N8 and MIL-N8 compounds. Furthermore, the thermogravimetric analysis demonstrated that MIL-N8 exhibits better stability than its precursor. Due to the structural attributes of MIL-N8 (containing both hydrophilic and hydrophobic moieties), it readily self-assembles into uniform nanostructures, such as micelles, at the critical aggregation concentration (CAC). This was further characterized through confocal microscopy using ANS as a fluorescent probe and visualized using TEM and FESEM imaging. These nanomicellar structures enabled the efficient encapsulation of the hydrophobic anticancer drug, quercetin (QCT), with high loading and sustained release behavior adhering to the Korsmeyer-Peppas model, which suggests diffusion-controlled transport through aggregated micellar layers. Furthermore, biological evaluation using SW-480 colon cancer cells demonstrated a remarkable enhancement in the anticancer activity of QCT-encapsulated and delivered via MIL-N8, moreover, in comparison to free QCT, the QCT-MIL-N8 formulation produced substantially lower IC50 values and pronounced dose and time-dependent effects. QCT-MIL-N8 formulation demonstrated increased apoptotic features, including nuclear condensation, fragmentation, and an increase in AO/EtBr-positive cells, as well as elevated intracellular ROS levels, that further supported oxidative stress-driven cell death as the predominant mechanism. Collectively, MIL-N8 nanomicelles emerge as a highly effective, low-toxicity delivery platform that significantly improves the therapeutic potential and controlled release of QCT for anticancer applications.