Intracellular delivery of cytochrome c by galactosylated albumin to hepatocarcinoma cells
Journal
Journal of Drug Targeting
Journal Volume
22
Journal Issue
6
Pages
528-535
Date Issued
2014
Author(s)
Abstract
In some cancer cells, translocation of cytochrome c (Cyt c) from mitochondria to the cytoplasma is inhibited. This inhibition prevents cells from undergoing apoptotic cell death and can lead to uncontrolled cell growth. Increasing cytoplasmic concentration of Cyt c can induce apoptosis in cancer cells as a strategy of cancer therapy. Here we proposed a galactosylated albumin based carrier for intracellular delivery of Cyt c to hepatocarcinoma cells. Galactosylated albumin is recognized by highly expressed asialoglycoprotein receptors (ASGPR) on hepatocarcinoma cells and is further internalized into cells via receptor mediated endocytosis. Cyt c was chemically conjugated to galactosylated albumin with a reducible disulfide linker in order to release Cyt c from the carrier inside cells. We tested cellular uptake and cytotoxicity of Cyt c conjugates in ASGPR positive and negative hepatocarcinoma cells. The results showed galatosylated albumin significantly increased cellular uptake in both cell types resulting in cytotoxicity in a dose dependent manner through the induction of apoptosis. The lack of ASGPR specific uptake might be due to other carbohydrate-recognizing receptors expressed on tumor cells. In general, our work has shown that intracellular delivery of Cyt c to tumor cells can be an alternative therapeutic approach and galactosylated albumin can be a protein drug carrier for intracellular delivery. ? 2014 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.
Subjects
Albumin; ASGPR; Cytochrome c; Hepatocarcinoma; Intracellular protein delivery
SDGs
Other Subjects
albuminoid; asialofetuin; cytochrome c; drug carrier; galactosamine; galactosylalbumin; unclassified drug; albuminoid; cytochrome c; galactose; article; carcinoma cell; confocal microscopy; controlled study; drug conjugation; drug cytotoxicity; endocytosis; enzyme activity; flow cytometry; gene translocation; human; human cell; internalization; limit of detection; liver cell carcinoma; molecular weight; particle size; polyacrylamide gel electrophoresis; priority journal; Western blotting; apoptosis; chemistry; liver tumor; mass spectrometry; metabolism; pathology; tumor cell line; Albumins; Apoptosis; Cell Line, Tumor; Cytochromes c; Galactose; Humans; Liver Neoplasms; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Type
journal article