Dual-Stimuli Chemotherapeutic Delivery From Magnetic Bacterial Nanocellulose: Unraveling the Optimized Loading and...

To maximize the delivery of doxorubicin (DOX) in cancer microenvironments, the dual-stimuli magnetic bacterial cellulose (m-BC) scaffolds are designed for optimized DOX interactions, localized internal heating (IH) and tailored wetting during release. The m-BC components, including surfactant (oleic acid; OA) and in situ synthesized magnetic nanoparticles (MNPs), not only drastically increased the loading efficiency (95.5 ± 2.5%) but significantly altered their pH-responsiveness through on-demand release. The localized IH effect on OA-mediated interactions in m-BCs accelerated DOX release, markedly distinct from external heating effects. DOX release from m-BCs is found to be driven by synergistic thermal distortions and protonation, where localized IH significantly enhance distortions (at 46 °C) and acidic media effectively enable protonation (at 38 °C). Notably, the on-demand DOX release is achieved at elevated IH conditions (46 °C, 3 cycles) by surpassing the programmed pH-responsive mechanism and reaching over 50% DOX release in pH 4.5, matching their release in pH 1.5. The superior dual responsiveness in such m-BCs enables high susceptibility to both pH and IH, releasing the same amount even in mildly acidic environments, independent of pH. This work not only thoroughly investigates the loading/release mechanisms, but opens further pathways to microenvironment-specific magnetothermal-chemotherapeutic delivery from BC-based multifunctional scaffolds.