Acidic pH-Triggered Drug Eluting Nanocomposites for MRI Monitored Intra-Arterial Drug Delivery to Hepatocellular Carcinoma.

Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter intra-arterial delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. Drug loading/release from DEB can be difficult to control and monitor the selective delivery to the targeted tumors. Embolized DEBs in hepatic artery frequently induce hypoxic and low pH condition promoting cancer cell growth. In this study, an acidic pH-triggered drug eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails (Octadecylamine-p(API-L-Asp)10) was developed for magnetic resonance imaging (MRI)-monitored transcatheter sorafenib (the only FDA-approved systemic therapy for liver cancer) delivery to hepatocellular carcinoma (HCC). The synthesized sorafenib loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic intra-arterial (IA) delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA delivered sorafenib loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib-pH-DENs platform has the potential to be used as an advanced tool for liver-directed intra-arterial treatment of unresectable HCC.