Focused ultrasound programmed characteristic NIR-IIb lanthanide mechanoluminescence for high sensitivity bioimaging in vivo

Optical imaging techniques for biodetection are hindered by limited sensitivity and resolution in deep tissues, arising primarily from photon scattering and endogenous autofluorescence. Herein, we report a focused ultrasound (FUS) programmable NIR-IIb emissive mechanoluminescent nanoparticle for in vivo bioimaging. Specifically, CaZnOS nanoparticles co-doped with Mn2+ and Er3+ were engineered to exhibit mechanoluminescence (ML) emission peaked at 1550 nm. FUS stimulation elicits ML without the need for optical excitation, thereby enabling deep-tissue imaging devoid of background interference from excitation light. By modulating the excitation frequency of FUS, ML can be programmed as a characteristic signal. Integrated with a Fourier frequency-transform identification reconstruction (FFIR) algorithm, the specific ML signals can be detected with high sensitivity, reaching sub-millimeter spatial resolution and markedly enhanced signal-to-background ratios compared to conventional photoluminescence-based approaches. By macrophage internalization of the ML nanoparticles to yield functional macrophage-nanoparticle (FMNs), a ultralow detection limit of 10 cells can be achieved. In murine tumor models, the FMNs facilitated real-time monitoring of early-stage tumor progression, underscoring their biocompatibility and translational promise for high-precision diagnostics in deep-seated neoplasms.