Targeted and synergistic therapy for hepatocellular carcinoma: monosaccharide modified lipid nanoparticles for the co-delivery of doxorubicin and sorafenib

Autor: Yan Liu, Wendu Duan
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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