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

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.

Janus Microcarriers for Magnetic Field‐Controlled Combination Chemotherapy of Hepatocellular Carcinoma

“…The deposition of the Janus microcarriers in the rim region of tumor is further confirmed by the presence of iron in tissues stained with Prussian Blue (Figure b). The distribution of Janus microcarriers are good agreement with previous results of IA infused microspheres . The deposited Janus microcarriers in tumor‐feeding arteries permit a controlled release of drugs into the tumor blood vessels.…”

“…For the magnetic anisotropy, iron oxide nanocubes with an average size of 27 nm are dispersed in the emulsion drops. The iron oxide nanocubes are synthesized by thermal decomposition of iron‐oleate complex in a mixture of sodium oleate, n ‐docosane, and 1‐octadecene and the surface is capped with oleic acid (Figure d and Figure S4, Supporting Information) . In addition, dual chemo agents of regorafenib and doxorubicin are dissolved in the emulsion drops.…”

Immunomodulatory Magnetic Microspheres for Augmenting Tumor-Specific Infiltration of Natural Killer (NK) Cells

“…The IONC loading efficacy within the IMM-MS was roughly 65%, which was consistent with our previous report. 19 As shown in Figure 2, IMM-MS exhibited much slower initial burst compared to control MS, whereas ~75% of IFN- γ was released from control MS in 1 h, IMM-MS released only ~27% of IFN- γ in 1 h. Furthermore, IMM-MS showed sustained drug release behavior over the entire test period. The sustained drug release behavior could be attributed to the water channel blocking by the addition of the iron oxide nanoparticles.…”

“…The shape and the physicochemical properties were consistent with our previous paper. 19 Next, the as-synthesized iron oxide nanocubes and IFN- γ were coencapsulated in PLGA microspheres (i.e., IMM-MS) via a double emulsion method. Spherical-shaped microparticles were clearly observed with optical microscopy (Figure 1b).…”

Preparation of microspheres encapsulating sorafenib and catalase and their application in rabbit VX2 liver tumor

“…Therefore, it is urgent to inhibit tumor angiogenesis in the treatment of TACE. Sorafenib (SOR), a multi-target tyrosine kinase inhibitor with the ability to inhibit angiogenesis and tumor proliferation, and is the only Food and Drug Administration (FDA) approved drug for the treatment of advanced HCC [11]. However, due to the lack of tumor specificity, oral-systemic administration of sorafenib often leads to high toxicity and severe side effects [12].…”