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Dual ligands modified double targeted nano-system for liver targeted gene delivery
Fanbo Jing1, Jing Li, Donghua Liu
1Department of Pharmacy, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, China. fanbo.jing@yahoo.com.cn
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.
Insights
This study developed dual-ligand modified nanocarriers for targeted gene delivery. The novel system effectively targets both cancer cells and liver macrophages, showing improved transfection efficiency.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Gene Therapy
Background:
- Nanocarrier surface modification with specific ligands creates a unique biological identity.
- Ligand-decorated nanocarriers enhance targeting and internalization into specific cell populations like cancer cells and diseased organs.
Purpose of the Study:
- To engineer a systemically administrable dual-ligand modified nanocarrier system.
- To achieve simultaneous targeting of both cancer cells and liver macrophages.
Main Methods:
- Synthesized transferrin-PEG-PE (T-PEG-PE) and mannan-PE (M-PE) ligands.
- Modified nanocarrier surfaces with these dual ligands (D-modified).
- Evaluated in vivo transfection efficiency in tumor-bearing animal models.
Main Results:
- Dual-ligand modified solid lipid nanoparticles (D-SLN/pEGFP) showed a particle size of 198 nm and 89% gene loading.
- Achieved over 25% higher transfection efficiency in HepG2 cells compared to M-SLN/pEGFP.
- Demonstrated enhanced transfection in Kupffer cells (KCs) compared to T-SLN/pEGFP.
Conclusions:
- Transferrin-PEG-PE and mannan-PE act as effective active targeting ligands.
- Dual-ligand modification significantly improves nanocarrier cell targeting ability.
- The developed dual-ligand nanocarriers show promise as an active targeting gene delivery system.
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