Dual-Targeted Lactoferrin Shell-Oily Core Nanocapsules for Synergistic Targeted/Herbal Therapy of Hepatocellular Carcinoma
| Autor: | Maged W. Helmy, Jia-You Fang, Shaza M Kamel, Mohammad A. Abdulkader, Amira Zaky, Ahmed O. Elzoghby, Mona A. Abdelmoneem, Kadria A. Elkhodairy, Manar A. Elnaggar, Ruwan S Hammady |
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| Rok vydání: | 2019 |
| Předmět: |
Sorafenib
Materials science Carcinoma Hepatocellular Combination therapy 02 engineering and technology Disaccharides 01 natural sciences Nanocapsules Mice Drug Delivery Systems In vivo 0103 physical sciences medicine Animals Humans General Materials Science Diethylnitrosamine Receptor 010304 chemical physics biology Lactoferrin Asialoglycoprotein Liver Neoplasms NF-kappa B Hep G2 Cells 021001 nanoscience & nanotechnology medicine.disease Gene Expression Regulation Neoplastic Ki-67 Antigen Cancer research biology.protein Glycyrrhetinic Acid 0210 nano-technology Liver cancer medicine.drug Phytotherapy |
| Zdroj: | ACS applied materialsinterfaces. 11(30) |
| ISSN: | 1944-8252 |
| Popis: | Herein, both strategies of synergistic drug combination together with dual active tumor targeting were combined for effective therapy of hepatocellular carcinoma (HCC). Therefore, based on the tumor sensitizing action, the herbal quercetin (QRC) was co-delivered with the targeted therapeutic drug sorafenib (SFB), preformulated as phospholipid complex, via protein shell-oily core nanocapsules (NCs). Inspired by the targeting action of lactoferrin (LF) via binding to LF receptors overexpressed by HCC cells, LF shell was electrostatically deposited onto the drug-loaded oily core to elaborate LF shell-oily core NCs. For dual tumor targeting, lactobionic acid (LA) or glycyrrhetinic acid (GA) was individually coupled to LF shell for binding to asialoglycoprotein and GA receptors on liver cancer cells, respectively. Compared to LF and GA/LF NCs, the dual-targeted LA/LF-NCs showed higher internalization into HepG2 cells with 2-fold reduction in half-maximal inhibitory concentration compared to free combination therapy after 48 h. Moreover, dual-targeted LF-NCs showed powerful in vivo antitumor efficacy. It was revealed as significant downregulation of the mRNA expression levels of nuclear factor-kappa B and tumor necrosis factor α as well as suppression of Ki-67 protein expression level in diethylnitrosamine (DEN)-induced HCC mice (P < 0.05). Furthermore, dual-targeted LF-NCs attenuated the liver toxicity induced by DEN in animal models. Overall, this study proposes dual-targeted LF-NCs for combined delivery of SFB and QRC as a potential therapeutic HCC strategy. |
| Databáze: | OpenAIRE |
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