Construction of in-situ self-assembled agent for NIR/PET dual-modal imaging and photodynamic therapy for hepatocellular cancer

Hepatocellular cancer (HCC) remained a life-threatening carcinoma. Agents for HCC imaging and therapy were expected to possess different intratumoral retention time. To construct an agent with different intratumoral retention time when applied for tumor imaging or therapy remained great values. A lasialoglycoprotein receptor (ASGPR) targeted lactobionic acid derivative (LABO) was constructed for fluorescent imaging and photodynamic therapy of HCC. ¹⁸F labeled LABO (¹⁸F-LABO) was developed for PET imaging of HCC. LABO and ¹⁸F-LABO showed similar molecular structure. LABO exhibited characteristic of viscosity and concentration-induced intratumoral in-situ self-assembly to expand the intratumoral retention. LABO was non-fluorescent at free stage, but emitted NIR fluorescence and generated irradiation-induced ROS after self-assembly for fluorescent imaging and photodynamic therapy. ASGPR specificity of LABO and ¹⁸F-LABO was confirmed using HepG2 cell. Biodistribution and fluorescent imaging confirmed the different tumor retention time of LABO and ¹⁸F-LABO when used for photodynamic therapy and PET imaging. PET imaging and photodynamic therapy were performed on HepG2 tumor bearing mice, which revealed that ¹⁸F-LABO/LABO could specifically accumulated in the HepG2 tumor for tumor location/inhibition. LABO/¹⁸F-LABO with excellent HCC specificity but different intratumoral behaviors showed great values for the PET/NIR imaging and photodynamic therapy for HCC.