Precise tumor resection under the navigation of Tumor- Microenvironment pH-activated NIR-II fluorescence imaging via calcium Carbonate/Polydopamine Co-packed Nd-doped downshifting nanoprobes

Photobleaching resistance, high quantum yield and deep tissue imaging of Nd-doped nanocrystals with fluorescence in the second near infrared region (NIR-II, 1000-1700 nm) occupied an indispensable posi-tion for precisely navigating tumor resection. However, these NIR-II nanoprobes often encounter high passive accumulation in reticuloendothelial system (RES) organs that attenuates signal to background ratio (SBR), resulting in the impediment of their application for accurate tumor outline delineation. Herein, a hollow-structured CaCO3 and polydopamine co-packed shell has been co-cladded on the Nd-doped down-shifting nanocrystals (DSNCs@hPCa). After conjugating folic acid molecules on the hollowed surface (DSNCs@hPCa-FA), this fascinating NIR-II contrast nanoagent can further specifically enhance tumor targeting capacity and gratifyingly restrain the NIR-II fluorescence in the "OFF" state. It sensitively responds to the weak acid tumor microenvironment, consequently, the hybrid nanoshell is degraded and the NIR-II fluorescence is efficiently turn "ON". Robust fluorescent imaging with the augmented SBR has been demonstrated to accurately identify tumor borderlines from normal tissue. Tumors were thoroughly removed under the navigation of this novel pH stimuli-responsive NIR-II fluorescence imaging with ignorable in situ recurrence or metastases after 28 days post-surgery. This strategy indicates the preclin-ical potential of tumor microenvironment activated nanoprobes for assisting the accurate delineation of tumor margins.& COPY; 2023 The Author(s). Published by Elsevier Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).