Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor-targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumor. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye makes it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, we developed Probe-1 to enhance PAI and PTT of liver tumor due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displayed 4.6-fold higher PA signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 showed extended retention time (10 h versus 6 h) and 2.1-fold higher PA signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increased 18°C (Tmax : 55°C) with 3.3-fold decreased volume while that in Group Probe-2 mildly increased 9.8°C (Tmax : 46.8°C) with 4.3-fold increased volume. We envision that our smart self-assembly strategy could be easily adjusted for PAI and PTT of more tumors. This article is protected by copyright. All rights reserved.

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