Brefeldin A delivery nanomicelles in hepatocellular carcinoma therapy: Characterization, cytotoxic evaluation in vitro, and antitumor efficiency in vivo.

Abstract

Hepatocellular carcinoma (HCC) is one of the major cancers with high mortality rate. Traditional drugs used in clinic are usually limited by the drug resistance and side effect and novel agents are still needed. Macrolide brefeldin A (BFA) is a well-known lead compound in cancer chemotherapy, however, with poor solubility and instability. In this study, to overcome these disadvantages, BFA was encapsulated in mixed nanomicelles based on TPGS and F127 copolymers (M-BFA). M-BFA was conferred high solubility, colloidal stability, and capability of sustained release of intact BFA. In vitro, M-BFA markedly inhibited the proliferation, induced G0/G1 phase arrest, and caspase-dependent apoptosis in human liver carcinoma HepG2 cells. Moreover, M-BFA also induced autophagic cell death via Akt/mTOR and ERK pathways. In HepG2 tumor-bearing xenograft mice, indocyanine green (ICG) as a fluorescent probe loaded in M-BFA distributed to the tumor tissue rapidly, prolonged the blood circulation, and improved the tumor accumulation capacity. More importantly, M-BFA (10 mg/kg) dramatically delayed the tumor progression and induced extensive necrosis of the tumor tissues. Taken together, the present work suggests that M-BFA has promising potential in HCC therapy.

• Authors: Jin-Man Zhang, Yao-Yao Jiang, Qun-Fa Huang, Xu-Xiu Lu, Guan-Hai Wang, Chang-Lun Shao, Ming Liu
• Journal: Pharmacological research (Pharmacol Res) Vol. 172 Pg. 105800 (10 2021) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 34363949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Micelles
• Polyethylenes
• Polypropylenes
• Vitamin E
• Brefeldin A
• UCON 50-HB-5100
• tocophersolan

Topics

• Animals
• Antineoplastic Agents (administration & dosage, blood, pharmacokinetics)
• Apoptosis (drug effects)
• Brefeldin A (administration & dosage, blood, chemistry, pharmacokinetics)
• Carcinoma, Hepatocellular (drug therapy, metabolism, pathology)
• Cell Line
• Cell Survival (drug effects)
• Female
• Humans
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Mice, Inbred BALB C
• Micelles
• Nanostructures (administration & dosage, chemistry)
• Polyethylenes (administration & dosage, chemistry)
• Polypropylenes (administration & dosage, chemistry)
• Rats, Sprague-Dawley
• Tissue Distribution
• Vitamin E (administration & dosage, chemistry)