NIR‐II Fluorescence and Magnetic Resonance Imaging‐Guided Efficient Piezodynamic Therapy of Subcutaneous Glioblastoma with a Biomimetic Nanoplatform Containing Defect‐Engineered Piezoelectric Shell and Downconversion Nanocore

Abstract Recent studies demonstrate that NIR‐II fluorescence imaging‐guided photodynamic therapy (PDT) is a promising paradigm for cancer theranostics, but its efficacy is suboptimal due to limited light penetration and oxygen dependence. Emerging piezodynamic therapy (PZDT) can overcome the shortcomings of PDT and shows merits including deep penetration, oxygen independence, and efficient reactive oxygen species (ROS) generation. Integration of NIR‐II fluorescence and PZDT can revolutionize cancer theranostics with greatly improved efficacy. However, it is difficult to achieve because of the optical darkness of piezoelectric materials. Herein, defect‐engineered NIR‐II transparent Gd‐doped KNbO 3 (GKNO) coating on NIR‐II fluorescent NaGd 0.65 F 4 @Nd 0.05 Yb 0.25 Er 0.05 downconversion nanocores, forming multifunctional nanoplatforms (DGKNO) for dual NIR‐II fluorescence/MR imaging‐guided PZDT. Importantly, Gd 3+ doping introduces interstitial defects in the KNO lattice, imparting MRI capability, bandgap widening, tenfold enhancement in piezoelectric coefficient, and enhanced ROS generation. Notably, bandgap widening enhanced NIR‐II transparency up to 96%, enabling effective NIR‐II fluorescence imaging. Furthermore, finite element analysis and first‐principle calculations validate the boosted piezoelectric effect and transparency. After cloaking with U87 glioma cell membranes to yield biomimetic nanoplatforms (CDGKNO), intravenous administration enabled NIR‐II fluorescence/MRI‐guided PZDT, inducing ROS‐mediated oxidative stress and macrophage polarization (M2 to M1), achieving efficient tumor inhibition. This work demonstrates dual NIR‐II fluorescence/MRI‐guided PZDT as a powerful paradigm for cancer treatment.