Dual-responsive chitosan/alginate magnetic nanoparticles for sequential chemo-photothermal therapy of glioblastoma

Glioblastoma (GBM) is among the most aggressive malignancies, with limited treatment success due to its invasiveness and resistance to conventional therapies. To address these challenges, we developed a dual-functional nanoplatform composed of curcumin diethyl disuccinate (CDD)-loaded chitosan/alginate-coated magnetic nanoparticles (CS/ALG-MNPs) for sequential chemo-photothermal therapy. This system integrates near-infrared (NIR)-responsive photothermal therapy (PTT) with pH-triggered drug release, using superparamagnetic iron oxide nanoparticles as the core. The nanoparticles, averaging 260 nm in diameter, exhibited strong colloidal stability and a magnetization saturation (M_s) of 57 emu/g, confirming their superparamagnetic nature. The formulation enabled efficient encapsulation and controlled release of CDD, achieving 88.7 ± 1.4% cumulative drug release at pH 5.3. In vitro studies in U87 glioblastoma cells demonstrated that CDD-CS/ALG-MNPs reduced the IC₅₀ by 41% compared to free CDD, due to enhanced cellular uptake under magnetic guidance and pH-sensitive release. Upon NIR irradiation, the nanoplatform reached 42.7 ± 0.05 °C and exhibited a photothermal conversion efficiency of 37.12%. The combined chemo-photothermal treatment led to a significant reduction in cell viability to ∼20%, while non-irradiated samples still showed notable cytotoxicity from the released drug. These findings highlight a stepwise treatment paradigm in which the chemotherapeutic component sensitizes tumor cells for enhanced photothermal ablation. The CDD-CS/ALG-MNP platform demonstrates high potential as a versatile strategy for glioblastoma therapy and supports broader applications involving other hydrophobic therapeutics.