Development of Dual-Responsive Magnetic/NIR-Triggered Multilayer Microcapsules for Controlled Methotrexate Delivery in Cancer Therapy

Near-infrared (NIR)-responsive drug delivery systems offer precise spatiotemporal control for targeted cancer therapy with minimal invasiveness. Here, we report the design of magnetic/NIR-responsive multilayer microcapsules via layer-by-layer assembly of biocompatible chitosan (CS) and carboxymethyl cellulose (CMC). Incorporation of magnetite (Fe₃O₄) and gold nanoparticles (Au NPs) into the microcapsule shells enabled both magnetic guidance and efficient NIR-triggered drug release. Methotrexate (MTX), a potent anti-cancer agent, was encapsulated with a high loading efficiency (68%). Systematic studies revealed the influence of bilayer number, MTX concentration, and environmental pH on drug loading and release kinetics. In vitro drug release was studied in different pH values and in the presence of an NIR irradiation. While the drug releases much faster in an acidic environment (pH 5.0) compared to physiological pH (7.4), it maintains stable release across both conditions, leading to uniform therapeutic delivery. Under NIR irradiation for15 min, up to 85% of the loaded MTX was released, while less than 7% was released when incubated in the dark for the same duration, significantly enhancing cytotoxicity against MCF-7 breast cancer cells. These dual-responsive microcapsules offer a versatile platform for targeted chemotherapy and photothermal therapy, highlighting their potential in minimally invasive cancer treatment.