Journal
PHARMACEUTICAL BIOLOGY
Volume 51, Issue 5, Pages 643-649Publisher
INFORMA HEALTHCARE
DOI: 10.3109/13880209.2012.761245
Keywords
Gene therapy; mannan; modification; solid lipid nanoparticles; transferrin
Funding
- Natural Science Foundation of Shandong Province [ZR2011HQ032, ZR2011HM030]
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Context: It is now well established that the surface of nanocarriers with specific ligands defines a new biological identity, which assist in targeting and internalization of the nanocarriers to specific cell populations, such as cancers and disease organs. Objective: The aim of this study is to develop systemically administrable dual ligands modified nano-system which could both target cancer cells and macrophages in the liver. Methods: Transferrin (Tf) and mannan (M) were linked onto polyethylene glycol-phosphatidylethanolamine (PEG-PE) and PE separately to get transferrin-PEG-PE (T-PEG-PE) and mannan-PE (M-PE) ligands for the surface modification of carriers. The in vivo transfection efficiency of the novel dual ligands modified (D-modified) vectors were evaluated in tumor bearing animal models. Results: D-modified solid lipid nanoparticles/enhanced green fluorescence protein plasmid (D-SLN/pEGFP) has a particle size of 198 nm and a gene loading quantity of 89%. D-SLN/pEGFP displayed over 25% higher transfection efficiency than M-PE modified SLN/pEGFP (M-SLN/pEGFP) in HepG2 cells and T-PEG-PE modified SLN/pEGFP (T-SLN/pEGFP) in Kupffer cells (KCs) isolated from mice. Conclusion: It could be concluded that T-PEG-PE and M-PE could function as excellent active targeting ligands to improve the cell targeting ability of the carriers and the dual ligands modified vectors could be applied as a promising active targeting gene delivery system.
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