Dual‐Stimuli Chemotherapeutic Delivery From Magnetic Bacterial Nanocellulose: Unraveling the Optimized Loading and Release at Tailored Wetting and Localized Heating

Abstract 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.