Chondroitin-modified lipid nanoparticles target the Golgi to degrade extracellular matrix for liver cancer management.

Liver cancer is a serious liver disease in which hepatoma cells and activated hepatic stellate cells (HSCs) overproduce extracellular matrix (ECM), which involves the Golgi apparatus. Here chondroitin-modified lipid nanoparticles (CSNs) were prepared and loaded with doxorubicin (DOX) and retinoic acid (RA) using a thin-film hydration-high pressure homogenization method. The resulting DOX + RA-CSNs were efficiently taken up by SMMC-7721 hepatoma cells and HSCs in culture, where they accumulated in the Golgi apparatus and destroyed it, inhibiting ECM production. Injecting DOX + RA-CSNs into mice with primary liver cancer or H22 allografts led to significantly higher tumor penetration by DOX and RA, greater antitumor efficacy, and lower DOX-related toxicity than injecting a solution of the two drugs. Immunofluorescence and immunohistochemistry of liver tissues showed that DOX + RA-CSNs dramatically reduced expression of the ECM components. These results suggest that CSNs show potential for targeting drugs to the Golgi apparatus of liver cancer cells and potentially other types of tumors.