Promising Nanoparticles-Based Oral Therapy for Effective Inhibition of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Portal vein tumor thrombus (PVTT) is a poor prognostic factor for hepatocellular carcinoma (HCC) patients, highlighting the need for an oral drug delivery system that combines convenience, simplicity, biosafety, and improved patient compliance. Leveraging the unique anatomy of the portal vein and insights from single-cell RNA sequencing of the PVTT tumor microenvironment, we developed oral pellets using CaCO@PDA nanoparticles (NPs) encapsulating both doxorubicin hydrochloride and low molecular weight heparin. These NPs target the tumor thrombus microenvironment, aiming to break down the thrombus barrier and turn the challenge of portal vein blockage into an advantage by enhancing drug delivery efficiency through oral administration. The NPs-based oral delivery system achieved excellent antitumor effects with minimal side effects, demonstrating a promising strategy for managing PVTT in advanced HCC and addressing tumor types associated with vascular invasion and hypercoagulability.