An Integrated Therapeutic Delivery System for Enhanced Treatment of Hepatocellular Carcinoma

Nanomaterials hold promise for the treatment of human carcinomas but integrating multiple functions into a single drug carrier system remains challenging. Herein, an integrated therapeutic delivery system for human hepatocellular carcinoma (HCC) treatment is reported, which is based on rhodamine B (RhB) end-labeled cationic poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) and hydrophobic poly(3-azido-2-hydroxypropyl methacrylate) (PGMA-N-3) segments equipped with a covalently bound galactose. This biocompatible and safe platform RhB-PDMAEMA25-c-PGMA50-Gal micelles (Gal-micelles) offers four advantages: (1) Galactose ligands enhance cellular uptake by targeting the asialoglycoprotein receptor (ASGPR) that is overexpressed on HCC cell lines surfaces; (2) RhB end-labeling facilitates real-time imaging for tracking both in vitro and in vivo; (3) the acidic tumor microenvironment protonates the carrier system for efficient drug release as well as gene transfection, (4) codelivery of anticancer drug doxorubicin (DOX) and B-cell lymphoma 2 small interfering RNA (Bcl-2 siRNA) works synergistically against tumor growth in both subcutaneous and orthotopic HCC bearing mouse models. This integrated therapeutic delivery system holds potential for future clinical HCC treatment.