A bubble-enhanced lanthanide-doped up/down-conversion platform with tumor microenvironment response for dual-modal photoacoustic and near-infrared-II fluorescence imaging.

We designed and constructed a nanoparticle LDNP@DMSN-Au@CaCO 3 (LDAC NPs) that integrates lanthanide-doped nanoparticles, Au NPs and CaCO 3 layer to achieve PAI/ NIR-II FI dual-mode imaging under 980 nm radiation. Under the excitation of 980 nm, LDNPs simultaneously implement the up/down-conversion, which not only can realize bright NIR-II FI, but also can provide the energy required for PAI of Au NPs through the fluorescence resonance energy transfer effect. In addition, the CaCO 3 layer can degrade under the tumor microenvironment and produce CO 2 microbubbles, which further enhance the PA signal through the bubble cavitation effect, thus improving the imaging effect. [Display omitted] As an important tumor diagnosis strategy in precision medicine, multimodal imaging has been widely studied. However, the weak imaging signal with low spatial resolution and the constant signal of lack of specific activation severely limit its disease diagnosis. Herein, a bubble-enhanced lanthanide-based up/down-conversion platform with tumor microenvironment response for dual-mode imaging, LDNP@DMSN-Au@CaCO 3 nanoparticles (named as LDAC NPs) were successfully developed. Combining the advantages of photoacoustic imaging (PAI) and the second near-infrared window (NIR-II) fluorescence imaging (FI), significantly improved the accuracy of diseases diagnosis. LDAC NPs with flower-like structure were synthesized through the encapsulation of uniform lanthanide-doped nanoparticles (NaYbF 4 :Ce,Er@NaYF 4 named LDNPs) with dendritic mesoporous silica (DMSN). The gold nanoparticles (Au NPs) were then in situ grown on the surface of DMSN and the surface were finally coated with a layer of calcium carbonate (CaCO 3). Under the excitation of the 980 nm laser, LDNPs showed strong emission of NIR-II at 1550 nm due to the doping of Ce and Er ions, showcasing excellent spatial resolution and deep tissue penetration characteristics, while the resulting visible light emission (540 nm) enables Au NPs to generate PAI signals with the aid of LDNPs via the fluorescence resonance energy transfer effect. In acidic tumoral environment, CaCO 3 layer could produce CO 2 microbubbles, and the PAI signals of LDAC NPs could be further enhanced with the generation of CO 2 bubbles due to the bubble cavitation effect. Simultaneously, the NIR-II FI of LDAC NPs was self-enhanced with the degradation of the CaCO 3. This intelligent nanoparticle with stimulus-activated dual-mode imaging capability holds great promise in future precision diagnostics. [ABSTRACT FROM AUTHOR]