Targeted and synergistic therapy for hepatocellular carcinoma: monosaccharide modified lipid nanoparticles for the co-delivery of doxorubicin and sorafenib
Autor: | Yan Liu, Wendu Duan |
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Rok vydání: | 2018 |
Předmět: |
N-acetylgalactosamine
Pharmaceutical Science 02 engineering and technology Mice Drug Delivery Systems Liver Neoplasms Experimental 0302 clinical medicine Drug Discovery Original Research Drug Carriers Mice Inbred BALB C Chemistry Liver Neoplasms Monosaccharides hepatocellular carcinoma Hep G2 Cells Sorafenib Prodrug 021001 nanoscience & nanotechnology Lipids 030220 oncology & carcinogenesis Hepatocellular carcinoma prodrug 0210 nano-technology Liver cancer medicine.drug Carcinoma Hepatocellular Mice Nude Antineoplastic Agents Structure-Activity Relationship 03 medical and health sciences asialoglycoprotein receptor In vivo Cell Line Tumor medicine Carcinoma Animals Humans Doxorubicin pH sensitive Cell Proliferation Pharmacology Drug Design Development and Therapy Dose-Response Relationship Drug medicine.disease Cancer research Nanoparticles Asialoglycoprotein receptor Drug Screening Assays Antitumor |
Zdroj: | Drug Design, Development and Therapy |
ISSN: | 1177-8881 |
Popis: | Wendu Duan, Yan Liu Department of Hepatobiliary Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei Province 071000, People’s Republic of China Purpose: Targeted hepatocellular carcinoma therapy was carried out to improve the efficacy of liver cancer treatment. The purpose of this study was to design an N-acetylgalactosamine (NAcGal) modified and pH sensitive doxorubicin (DOX) prodrug (NAcGal-DOX) for the construction of lipid nanoparticles (LNPs). Methods: NAcGal-DOX and sorafenib (SOR) co-loaded LNPs were designed and the synergistic effects were evaluated on human hepatic carcinoma (HepG2) cells in vitro and anti-hepatic carcinoma mice model in vivo. Results: Cellular uptake efficiency of NAcGal modified LNPs was significantly higher than unmodified LNPs. NAcGal modified LNPs showed the most significant inhibition effect among all the samples tested. The results revealed that the LNPs system achieved significant synergistic effects, best tumor inhibition ability and the lowest systemic toxicity. Conclusion: These results proved that the NAcGal conjugated and pH sensitive co-delivery nano-system could be a promising strategy for treatment of hepatocellular carcinoma. Keywords: hepatocellular carcinoma, asialoglycoprotein receptor, N-acetylgalactosamine, pH sensitive, prodrug |
Databáze: | OpenAIRE |
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