SiRNA-phospholipid conjugates for gene and drug delivery in cancer treatment.

Abstract

Due to low charge density and stiff backbone structure, small interfering RNA (siRNA) has inherently poor binding ability to cationic polymers and lipid carriers, which results in low siRNA loading efficiency and limits siRNA success in clinical application. Here, siRNA-phospholipids conjugates are developed, which integrate the characteristics of the two phospholipids to self-assemble via hydrophilic siRNA and hydrophobic phospholipid tails to overcome the siRNA's stiff backbone structures and enhance the siRNA loading efficiency. In this study, the thiol-modified sense and antisense siRNA are chemically conjugated with phospholipids to form sense and antisense siRNA-phospholipid, and then these sense or antisense siRNA-phospholipids with equal amounts are annealed to generate siRNA-phospholipids. The siRNA-phospholipids can serve dual functions as agents that can silence gene expression and as a component of nanoparticles to embed hydrophobic anticancer drugs to cure tumor. siRNA-phospholipids together with cationic lipids and DSPE-PEG2000 fuse around PLGA to form siRNA-phospholipids enveloped nanoparticles (siRNA-PCNPs), which can deliver siRNAs and hydrophobic anticancer drugs into tumor. In animal models, intravenously injected siRNA-PCNPs embedded DOX (siPlk1-PCNPs/DOX) is highly effective in inhibiting tumor growth. The results indicate that the siRNA-PCNPs can be potentially applied as a safe and efficient gene and anticancer drug delivery carrier.

• Authors: Hongmei Liu, Yan Li, Anbu Mozhi, Liang Zhang, Yilan Liu, Xia Xu, Jianmin Xing, Xingjie Liang, Guanghui Ma, Jun Yang, Xin Zhang
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 24 Pg. 6519-33 (Aug 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24797882 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Phospholipids
• Proto-Oncogene Proteins
• RNA, Small Interfering
• Doxorubicin
• Protein Serine-Threonine Kinases
• polo-like kinase 1

Topics

• Animals
• Apoptosis (drug effects)
• Cell Cycle Proteins (metabolism)
• Cell Proliferation (drug effects)
• Doxorubicin (pharmacology, therapeutic use)
• Drug Delivery Systems
• Endocytosis (drug effects)
• Female
• Gene Knockdown Techniques
• Gene Silencing (drug effects)
• Gene Transfer Techniques
• HeLa Cells
• Humans
• In Situ Nick-End Labeling
• Mice, Inbred BALB C
• Mice, Nude
• Nanoparticles (chemistry, ultrastructure)
• Neoplasms (drug therapy)
• Phospholipids (chemical synthesis, metabolism)
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins (metabolism)
• RNA, Small Interfering (metabolism)