Doxorubicin-loaded glycyrrhetinic acid modified recombinant human serum albumin nanoparticles for targeting liver tumor chemotherapy.

Abstract

Due to overexpression of glycyrrhetinic acid (GA) receptor in liver cancer cells, glycyrrhetinic acid modified recombinant human serum albumin (rHSA) nanoparticles for targeting liver tumor cells may result in increased therapeutic efficacy and decreased adverse effects of cancer therapy. In this study, doxorubicin (DOX) loaded and glycyrrhetinic acid modified recombinant human serum albumin nanoparticles (DOX/GA-rHSA NPs) were prepared for targeting therapy for liver cancer. GA was covalently coupled to recombinant human serum albumin nanoparticles, which could efficiently deliver DOX into liver cancer cells. The resultant GA-rHSA NPs exhibited uniform spherical shape and high stability in plasma with fixed negative charge (∼-25 mV) and a size about 170 nm. DOX was loaded into GA-rHSA NPs with a maximal encapsulation efficiency of 75.8%. Moreover, the targeted NPs (DOX/GA-rHSA NPs) showed increased cytotoxic activity in liver tumor cells compared to the nontargeted NPs (DOX/rHSA NPs, DOX loaded recombinant human serum albumin nanoparticles without GA conjugating). The targeted NPs exhibited higher cellular uptake in a GA receptor-positive liver cancer cell line than nontargeted NPs as measured by both flow cytometry and confocal laser scanning microscopy. Biodistribution experiments showed that DOX/GA-rHSA NPs exhibited a much higher level of tumor accumulation than nontargeted NPs at 1 h after injection in hepatoma-bearing Balb/c mice. Therefore, the DOX/GA-rHSA NPs could be considered as an efficient nanoplatform for targeting drug delivery system for liver cancer.

• Authors: Wen-Wen Qi, Hai-Yan Yu, Hui Guo, Jun Lou, Zhi-Ming Wang, Peng Liu, Anne Sapin-Minet, Philippe Maincent, Xue-Chuan Hong, Xian-Ming Hu, Yu-Ling Xiao
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 12 Issue 3 Pg. 675-83 (Mar 02 2015) ISSN: 1543-8392 [Electronic] United States
• PMID: 25584860 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Nanocapsules
• Recombinant Proteins
• Serum Albumin
• Doxorubicin
• Glycyrrhetinic Acid

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Doxorubicin (administration & dosage, pharmacokinetics)
• Drug Delivery Systems
• Glycyrrhetinic Acid (chemistry)
• HeLa Cells
• Hep G2 Cells
• Humans
• Liver Neoplasms, Experimental (drug therapy, metabolism)
• Magnetic Resonance Spectroscopy
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Electron, Transmission
• Nanocapsules (administration & dosage, chemistry, ultrastructure)
• Recombinant Proteins (chemistry)
• Serum Albumin (chemistry)
• Tissue Distribution
• Xenograft Model Antitumor Assays