Abstract

Exogenous contrast agents have been extensively applied in photoacoustic (PA) molecular imaging for disease diagnosis, benefiting from their advantageous optical, thermal, and internal delivery properties. However, their in vivo performance was inevitably interfered by background tissue optical absorption, resulting in low imaging contrast and sensitivity. Here, we report a NIR-II femtosecond laser-induced nonlinearly enhanced PA imaging technique based on two-photon absorption of monolayer WS2-PVP nanosheets (NSs), which facilitates foreground extraction of the targeting region with the background signal being significantly suppressed. The optical nonlinearity of the monolayer WS2-PVP NSs was first demonstrated by a Z-scan system under the irradiation of a femtosecond laser to be 0.38, with an antithesis of virtually zero for the tissue-mimicking sample. Experiments on tissue-mimicking phantoms and in vitro chicken breast showed that the nonlinear PA enhancement of monolayer WS2-PVP NSs can facilitate foreground-extraction imaging at deep-seated position up to 4 mm. In addition, the in vivo foreground-extraction imaging ability by using monolayer WS2-PVP NSs was further demonstrated by mouse tumor models, where the tumor regions were specifically extracted with high imaging contrast. This work proposed a nonlinearly enhanced contrast mechanism of PA nanoprobes, prefiguring great potential for high-contrast and high-specificity PA molecular imaging.

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