Octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components to enhance tumor targeting and hepatoma therapy

Abstract

A nanosized drug delivery platform with a combination of rational components and tumor targeting is significant for enhancement of anticancer therapy and reduction of side effects. In this study, we developed a octanoyl galactose ester-modified microemulsion system self-assembled by coix seed components (Gal(oct)-C-MEs), which improved the tumor accumulation through asialoglycoprotein receptor-mediated endocytosis and promoted the antitumor efficacy through multicomponent-mediated synergistic effect. Octanoyl galactose ester (Gal(oct)) with a yield of 82.3% was synthesized through a green enzymatic reaction and multidimensional characterization. Gal(oct)-C-MEs with a spherical shape had a small and uniform particle size (58.49±1.03 nm), narrow polydispersity index (0.09±0.01) and neutral surface charge (−5.82±0.57 mV). In the cellular uptake studies, the internalized Gal(oct)-C-ME was 2.28-fold higher relative to that of coix seed component-based microemulsions (C-MEs). The half-maximal inhibitory concentration of Gal(oct)-C-MEs against HepG2 cells was 46.5±2.4 μg/mL, which was notably higher than that of C-MEs. Importantly, the intratumor fluorescence of HepG2 xenograft-bearing nude mice treated with Cy5/Gal(oct)-C-MEs was 1.9-fold higher relative to treatment with Cy5/C-MEs. In the study of antitumor efficacy in vivo, HepG2 xenograft-bearing nude mice intragastrically administered Gal(oct)-C-MEs for 14 days exhibited the strongest inhibition of tumor growth and the lowest toxicity against liver and kidney among all the treatments. In summary, Gal(oct)-C-ME, as a highly effective and safe anticancer drug delivery system, showed promising potential for hepatoma therapy.

Kanglaite reverses multidrug resistance of HCC by inducing apoptosis and cell cycle arrest via PI3K/AKT pathway

“…KLT has already been developed for anti-tumor clinical applications. 16 It is used to treat primary malignant tumors, including in lung cancer, liver cancer, gastric cancer, and breast cancer, because of its anti-proliferation and proapoptotic effects on numerous tumor cell lines in vitro and tumor models in vivo, 17 – 22 when it is combined with some chemotherapeutic agents.…”

Improved delivery of natural alkaloids into lung cancer through woody oil-based emulsive nanosystems

“…Furthermore, the anti-ovarian cancer activity of fructus bruceae oil was enhanced by being loaded into luteinizing hormone-releasing hormone receptor-targeted liposomes (Ye et al., 2016 ). In addition, coix seed oil can be carried by octanoyl galactose ester-modified intragastrical microemulsion for enhanced tumor targeting and hepatoma therapy (Qu et al., 2017 ). Fructus bruceae oil and coix seed oil loaded in an intravenous emulsion could be administered simultaneously for synergic antitumor application (Yu et al., 2008 ).…”

“…This is consistent with previous reports that microbubbles induced clathrin-mediated endocytosis and fluid-phase uptake through distinct mechanisms (Fekri et al., 2016 ) and that doxorubicin-conjugated poly(methacrylic acid- co -cholesteryl methacrylate) copolymers were internalized through both clathrin-dependent and clathrin-independent endocytosis mechanisms (Sevimli et al., 2015 ). However, octanoyl galactose ester-modified microemulsion systems containing coix seed components were reported to improve accumulation in tumors through asialoglycoprotein receptor-mediated endocytosis (Qu et al., 2017 ).…”

Lipid-Based Nanoparticles: Application and Recent Advances in Cancer Treatment

“…Furthermore, new nanoformulations are being developed and tested to increase the available antitumor strategies against LivC. For example, Lin et al [78] and Qu et al [79] developed two new MEs: (1) a CUR-loaded soybean-based ME, and (2) an ME based on Coix seed components (C-ME) modified with an octanoyl galactose ester to actively target the asialoglycoprotein receptor, overexpressed in hepatoma cells. The former was demonstrated to cause toxicity in HepG2 cells preferentially at low concentrations (15 μM), while the latter made it possible to increase both cellular internalization and cytotoxicity both in HepG2 cells and in HepG2 tumor xenograft-bearing mice.…”