Conjugates of lactobionic acid and IR820: New photosensitizers for efficient photodynamic therapy of hepatoma cells

New indocyanine green (IR820) is an indocyanine green analog which has attracted increasing attention in cancer phototherapy for the prominent absorbance at near-infrared region and improved stability. However, the lack of tumor targeting ability is still an obstacle that severely limits the application of IR820. Lactobionic acid (LA) is a ligand for the asialoglycoprotein receptors which are overexpressed on the membrane of hepatocellular carcinoma cells. In this work, three conjugates of LA and IR-820, namely LA-IR820, LA-SS-IR820, and LA-DEG-IR820, were developed for targeted photodynamic therapy of hepatocellular carcinoma (HCC). The in vitro photodynamic effect study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit similar singlet oxygen quantum yield as compared to free IR820. The cellular uptake study demonstrates that LA-IR820, LA-SS-IR820, and LA-DEG-IR820 exhibit enhanced cellular uptake amount as compared to free IR820 due to the ligand-receptor interactions between LA and asialoglycoprotein receptor overexpressed on the membrane of HepG2 cells. Among these three conjugates, LA-IR820 with hydrodynamic diameter of 154.6 ± 6.1 nm exhibits the highest cellular uptake amount. The cellular reactive oxygen species (ROS) generation study shows that LA-IR820, LA-SS-IR820 and LA-DEG-IR820 display enhanced cellular ROS level as compared to free IR820 and LA-IR820 exhibits the highest cellular ROS level upon 600 mW/cm 2 660 nm laser irradiation. As a result, LA-IR820, LA-SS-IR820 and LA-DEG-IR820 exhibit enhanced photocytotoxicity against HepG2 cells as compared to free IR820 and LA-IR820 exhibits the highest photocytotoxicity. LA-IR820, LA-SS-IR820, and LA-DEG-IR820 show significant potential for the targeted photodynamic therapy of HCC.