Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-Arterial Drug Delivery to Hepatocellular Carcinoma

Wooram Park, Jeane Chen, Soojeong Cho, Sin Jung Park, Andrew C. Larson*, Kun Na, Dong Hyun Kim

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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 IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, 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 delivery of sorafenib (the only FDA-Approved systemic therapy for liver cancer) to 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 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 IA treatment of unresectable HCC.

Original languageEnglish (US)
Pages (from-to)12711-12719
Number of pages9
JournalACS Applied Materials and Interfaces
Volume8
Issue number20
DOIs
StatePublished - May 25 2016

Keywords

  • hepatocellular carcinoma
  • image-guided therapy
  • iron oxide nanoparticles
  • nanocomposite microspheres
  • pH-responsive materials
  • sorafenib

ASJC Scopus subject areas

  • Materials Science(all)

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