Osteopontin targeted non-invasive nanoprobes with amplified surface plasmon resonance for photothermally enhanced multimodal precision imaging of vulnerable atherosclerotic plaques

•SAmOCP nanoplatform precisely target vulnerable atherosclerosis (AS) plaques.•SAmOCP nanoplatform enable non-invasive multimodal imaging for vulnerable AS plaques.•SAmOCP nanoplatform with excellent biosafety. Can be synthesized in large quantities and clinically translated. Effective strategies for accurate differentiation of the vulnerable atherosclerosis (AS) plaques at molecular level for clinical diagnosis have yet been developed. Herein, a versatile SAmOCP nanoprobe, is constructed by sealing up the multinuclear gold self-assembled nanospheres by hollow mesoporous silicon shell and then decorating the surfaces with Chlorine e6 (Ce6)-conjugated osteopontin antibody (OPN Ab), followed by filling the internal cavity with perfluoropentane (PFP) for precise in vivo targeting and multi-modal imaging of the vulnerable AS plaques. SAmOCP nanoprobes actively recognize the foam cells and specifically target the vulnerable AS plaques in vivo. Relying on the exceptional photo-to-heat conversion properties resulting from enhanced localized surface plasmon resonance (LSPR) effects of Au self-assembled particles, the encapsulated liquid PFP could transform into abundant microbubbles when AS plaque-rich regions were overheated by 808-nm laser irradiation, enabling hyperthermia-enhanced microbubbles generation, thereby endowing nanoprobes with significantly enhanced ultrasonic imaging capacity. SAmOCP nanoprobes exhibit a triple-modality diagnostic efficacy of ultrasound/fluorescence/photothermal imaging for in vivo precise detection of vulnerable AS plaques at molecular level. Together, SAmOCP nanoprobes overcome the difficulty in identifying the vulnerable AS plaque for clinic practice, holding great promise for vulnerable AS diagnosis.