Endogenous Shear‐Responsive Chemiluminescence Theranostics for Self‐Illuminating Thrombosis Imaging and Piezo‐Photodynamic Therapy

ABSTRACT Thrombotic diseases represent a major global health challenge, yet current theranostic systems suffer from bleeding risks, rapid agent clearance, and external irradiation reliance. To tackle these issues, we developed a shear stress‐responsive platform integrating endogenous piezoelectric thrombolysis and on‐site chemiluminescence imaging. Specifically, calcium‐/zirconium‐doped barium titanate (BCTZ) nanorods (NRs) modified with chlorin e6 (Ce6), luminol, and Arg‐Gly‐Asp (RGD) peptides, yielding BCTZ@CeLu‐R NRs. A strong correlation is demonstrated between piezoelectric potentials and the degree of stenosis, providing rational mechanical signals for stenosis‐adaptive thrombus imaging and thrombolysis. The shear force‐triggered piezocatalysis operates according to energy band theory, as evidenced by thoroughly monitoring degradation rates of various dyes in media with different pH values. Piezocatalysis of NRs primarily generates ·OH and ·O 2 − to oxidize luminol and generate chemiluminescence, which, in turn, activates Ce6 to emit fluorescence for imaging and producing 1 O 2 for photodynamic therapy (PDT), creating a piezocatalysis‐chemiluminescence‐energy transfer cascade. In a rat model of carotid artery thrombosis, RGD‐targeted NRs achieve four‐fold higher luminescence for deep‐tissue imaging without external excitation, and combined piezocatalysis, PDT, and RGD‐mediated targeting realize 97.7% thrombolysis efficiency. This work pioneers an innovative theranostic approach driven by endogenous shear force, enabling clot site‐specific and stenosis degree‐adaptive thrombosis imaging and thrombus dissolution.