TPGS-Based pH-Responsive Magnetic Nanomicelles for Synergistic Co-delivery of Doxorubicin and Curcumin in Astrocytoma Treatment

Developing multifunctional nanocarriers to overcome multidrug resistance (MDR) and enhance tumor accumulation remains a critical challenge in glioblastoma therapy. This study reports the engineering of a pH-responsive magnetic nanomicelle system (TPGS-Fe 3 O 4 -Dox-Cur-F127) for the synergistic codelivery of Doxorubicin (Dox) and Curcumin (Cur). The nanomicelles were constructed with a core–shell architecture, integrating superparamagnetic iron oxide (Fe 3 O 4 ) cores within a shell of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and Pluronic F127. This design utilizes TPGS for P-glycoprotein inhibition and F127 for steric stability. The resulting formulation exhibited a uniform spherical morphology with a mean diameter of 176 nm and high colloidal stability. The system exhibited dual functionality: magnetic hyperthermia potential with a specific absorption rate (SAR) of 86.7 W/g and a pH-triggered drug release profile governed by Fickian diffusion. This mechanism ensures accelerated drug release in the acidic tumor microenvironment while minimizing premature leakage at physiological pH. In vitro evaluation against human astrocytoma cells (CCF-STTG1) revealed significant antitumor efficacy with an IC 50 of 5.94 μg/mL, representing a 12-fold increase in potency compared to free drugs. Quantitative analysis confirmed a strong synergistic interaction between Dox and Cur (combination index, CI = 0.08). Furthermore, the nanosystem displayed a high selectivity index (SI = 14.73), indicating a widened therapeutic window and reduced toxicity toward normal cells. These findings highlight the potential of the TPGS-Fe 3 O 4 -Dox-Cur-F127 nanomicelles as a stable, safe, and effective theranostic platform for astrocytoma treatment.