期刊
ACS APPLIED MATERIALS & INTERFACES
卷 8, 期 20, 页码 12711-12719出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b03505
关键词
nanocomposite microspheres; iron oxide nanoparticles; pH-responsive materials; hepatocellular carcinoma; sorafenib; image-guided therapy
资金
- ACS (American Cancer Society) [ACS 279148]
- National Cancer Institute [R01CA141047, R21CA173491, R21EB017986, R21CA185274]
- National Institute of Biomedical Imaging and Bioengineering
- Center for Translational Imaging
- Mouse Histology and Phenotyping Laboratory at Northwestern University
- Basic Research Laboratory (BRL) Program through National Research Foundation of Korea (NRF) - Korean government (MSIP) [2015R1A4A1042350]
- National Research Foundation of Korea [2015R1A4A1042350] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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.
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