Anti-stromal nanotherapeutics for hepatocellular carcinoma

Hepatocellular carcinoma (HCC), the most commonly diagnosed primary liver cancer, has become a leading cause of cancer-related death worldwide. Accumulating evidence confirms that the stromal constituents within the tumor microenvironment (TME) exacerbate HCC malignancy and set the barriers to current anti-HCC treatments. Recent developments of nano drug delivery system (NDDS) have facilitated the application of stroma-targeting therapeutics, disrupting the stromal TME in HCC. This review discusses the stromal activities in HCC development and therapy resistance. In addition, it addresses the delivery challenges of NDDS for stroma-targeting therapeutics (termed anti-stromal nanotherapeutics in this review), and provides recent advances in anti-stromal nanotherapeutics for safe, effective, and specific HCC therapy.