Surface Engineering of Nanoparticles for Targeted Delivery to Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated deaths worldwide. There is a lack of efficient therapy for HCC; the only available first-line systemic drug, sorafenib, can merely improve the average survival by two months. Among the efforts to develop an efficient therapy for HCC, nanomedicine has drawn the most attention, owing to its unique features such as high drug-loading capacity, intrinsic anticancer activities, integrated diagnostic and therapeutic functionalities, and easy surface engineering with targeting ligands. Despite its tremendous advantages, no nanomedicine can be effective unless it successfully targets the tumor site, which is a challenging task. In this review, the features of HCC are described, and the physiological hurdles that prevent nanoparticles from targeting HCC are discussed. Then, the surface physicochemical factors of nanoparticles that can influence targeting efficiency are discussed. Finally, a thorough description of the physiological barriers that nanomedicine must conquer before uptake by HCC cells if possible is provided, as well as the surface engineering approaches to nanomedicine to achieve targeted delivery to HCC cells. The physiological hurdles and corresponding solutions summarized in this review provide a general guide for the rational design of HCC targeting nanomedicine systems.