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Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2020 Nov; Vol. 131, pp. 110682. Date of Electronic Publication: 2020 Sep 15. - Publication Year :
- 2020
-
Abstract
- Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity. Therefore, liver-targeting drug delivery systems have attracted considerable attention for the treatment of HCC. In this study, we explored the liver-targeting efficacy and antitumor effect of adenine-loaded glycyrrhetinic acid-modified hyaluronic acid (Ade/GA-HA) nanoparticles in vitro and in vivo. The GA-HA nanoparticles possessed obvious targeting specificity toward liver cancer cells, which was mainly achieved by the specific binding of the GA ligand to the GA receptor that was highly expressed on the liver cell membrane. In vitro and in vivo results showed that Ade/GA-HA nanoparticles could inhibit liver cancer cell proliferation and migration, promote apoptosis, and significantly inhibit the growth of tumor tissues. Altogether, this study is the first to successfully demonstrate that the targeting activity and antitumor effect of Ade against HCC are enhanced by using GA-HA nanoparticles in vitro and in vivo.<br /> (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Adenine metabolism
Animals
Anti-Inflammatory Agents administration & dosage
Anti-Inflammatory Agents metabolism
Carcinoma, Hepatocellular metabolism
Female
Glycyrrhetinic Acid metabolism
Hep G2 Cells
Humans
Liver Neoplasms metabolism
MCF-7 Cells
Mice
Mice, Inbred BALB C
Mice, Nude
Nanoparticles metabolism
Random Allocation
Rats
Rats, Sprague-Dawley
Tumor Burden drug effects
Tumor Burden physiology
Adenine administration & dosage
Carcinoma, Hepatocellular drug therapy
Drug Delivery Systems methods
Glycyrrhetinic Acid administration & dosage
Liver Neoplasms drug therapy
Nanoparticles administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 131
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 32947204
- Full Text :
- https://doi.org/10.1016/j.biopha.2020.110682