Targeted delivery of garcinia glycosides by reconstituted high-density lipoprotein nano-complexes

Abstract

Scavenger receptor class B type 1 (SR-B1) is over-expressed in tumour cells where it mediates the uptake of drug payload of reconstituted high density lipoprotein (rHDL) via the process of reverse cholesterol transport. In this study, rHDL was prepared to determine its function as a drug delivery carrier for targeting hepatocellular carcinoma by incorporating the anti-tumour drug garcinia glycosides (GG) into rHDL to yield rHDL/GG nano-complexes. Structural analysis indicated that the rHDL/GG nano-complex was similar to HDL in size. HepG2 cells treated with fluorescent-labelled rHDL/GG exhibited a time-dependent increase in cell death. Further experiment in which HepG2 cells were treated with rHDL/GG plus plasma-derived HDL showed reduction in cell death compared to treatment with rHDL/GG alone, suggesting that plasma-derived HDL compete with rHDL/GG for binding to the SR-B1 on the cell. We concluded that rHDL could not only incorporate GG but could also serve as a carrier, targeting the drug to HepG2 cells via SR-B1.

Keywords:

• High density lipoprotein
• garcinia glycosides
• scavenger receptor class B type I
• reconstituted high density lipoprotein
• nano-complexes

Acknowledgements

Garcinia glycosides was provided by College of Pharmacy of Liaoning University, New Drug R&D Key Laboratory of Liaoning Province. Special thank is given to Dr Alan K Chang (Wenzhou University) for his substantial contribution to the revision of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by grants from the Drug Discovery Initiative of the National 11th Five Year Plan (2009ZX09103–030) and Innovation Team Project (No: LT2015011) from the Department of Education of Liaoning Province.