Self-assembled biomimetic nanocomposite integrating defect-enhanced piezoelectricity with NIR-II fluorescence and MR imaging for ultrasound-triggered piezo/chemodynamic therapy of subcutaneous glioma

Multifunctional theranostic nanoplatforms enabling precise targeting and controlled deep tissue therapy are vital. Herein, we present a self-assembled, defect-engineered, biomimetic nanoplatform (CDMBBTO), in which piezoelectric material and downconversion nanoparticles (DCNPs) are co-assembled within a polymer matrix, preventing interactions between both components, thereby allowing each to retain its intrinsic properties while collectively enabling dual second near infrared fluorescence (NIR-II FL)/magnetic resonance (MR) imaging and synergistic piezo/chemodynamic therapy (PZDT/CDT). Mn/Bi codoped piezoelectric BaTiO 3 (MBBTO) NPs exhibit a significantly enhanced piezoelectric coefficient (~5 fold higher than pristine BTO) owing to bandgap modulation induced by defect engineering. The incorporated Mn 2+ not only catalyzes Fenton like reactions for sustained tumor suppression but also provides strong T 2 weighted MR contrast. Self-assembled NIR-II emissive DCNPs enable deep tissue optical imaging, forming an integrated theranostic system. Cloaking of U87 glioma cell membranes imparts homologous tumor targeting capability. In vivo dual modal imaging reveals efficient tumor accumulation, with peak NIR-II FL and MR signal intensities observed 6 h post-injection. Upon ultrasound activation, CDMBBTO elicits potent tumor ablation through synergistic reactive oxygen species generation and immune modulation, characterized by macrophage polarization (M2 → M1) and upregulation of proinflammatory cytokines (TNF-α and IL-6). This work establishes CDMBBTO as a powerful nanoplatform for dual modal imaging-guided, immune potentiated PZDT/CDT toward effective glioblastoma treatment.