Dual-Modal Imaging and Synergistic Spinal Tumor Therapy Enabled by Hierarchical-Structured Nanofibers with Cascade Release and Postoperative Anti-adhesion.

ABSTRACT

Most treatments for spinal cancer are accompanied by serious side effects including subsequent tumor recurrence, spinal cord compression, and tissue adhesion, thus a highly effective treatment is crucial for preserving spinal and neurological functionalities. Herein, trilayered electrospun doxorubicin@bovine serum albumin/poly(ε-caprolactone)/manganese dioxide (DOX@BSA/PCL/MnO2) nanofibers with excellent antiadhesion ability, dual glutathione/hydrogen peroxide (GSH/H2O2) responsiveness, and cascade release of Mn2+/DOX was fabricated for realizing an efficient spinal tumor therapy. In detail, Fenton-like reactions between MnO2 in the fibers outermost layer and intra-/extracellular glutathione within tumors promoted the first-order release of Mn2+. Then, sustained release of DOX from the fibers' core layer occurred along with the infiltration of degradation fluid. Such release behavior avoided toxic side effects of drugs, regulated inflammatory tumor microenvironment, amplified tumor elimination efficiency through synergistic chemo-/chemodynamic therapies, and inhibited recurrence of spinal tumors. More interestingly, magnetic resonance and photoacoustic dual-modal imaging enabled visualizations of tumor therapy and material degradation in vivo, achieving rapid pathological analysis and diagnosis. On the whole, such versatile hierarchical-structured nanofibers provided a reference for rapid and potent theranostic of spinal cancer in future clinical translations.