title: Intracellular delivery of cytochrome c by galactosylated albumin to hepatocarcinoma cells.
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.
authors.affiliation: School of Pharmacy and.
authors.forename: Tzyy-Harn
authors.initials: TH
authors.lastname: Yeh
authors.forename: Fe-Lin Lin
authors.initials: FL
authors.lastname: Wu
authors.forename: Li-Jiuan
authors.initials: LJ
authors.lastname: Shen
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000008:administration & dosage*; D005690:Galactose / Q000737:chemistry*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D000418:Albumins; D045304:Cytochromes c; D005690:Galactose
keywords: ASGPR; Albumin; cytochrome c; hepatocarcinoma; intracellular protein delivery