원문정보
초록
영어
Nanomedicine constitutes the emerging field of medical applications for nanotechnology such as nanomaterial-based drug delivery systems. This technology may hold exceptional potential for novel therapeutic approaches to liver diseases. Activ ation of apoptosis pathway is a key mechanism by which cytotoxic drugs kill tumor cells. Delivering drugs sele ctively to cancer cells but not to nearby normal cells is a major obstacle in drug therapy. In this study, lithoch olic acid (LCA), a potent anti-cancer drug, is converted to two forms of poly(ethyleneglycol) (PEG) conjugates, viz., PEG-LCA (PL) and lactobionic acid (LBA) conjugated PEG-LCA (LPL). The latter form contains a galacto se ligand in LBA to target the hepatocytes. Both forms are self-assembled to form nanoparticle formulation, and they have high potency than LCA to kill HepG2 cancer cells, sparing normal LO2 cells. Besides, LPL has high specificity to mouse liver cells in vivo after intravenous (IV) injection. Western blot results confirm that the cel l death is occurred through apoptosis induced by LPL nanoparticles. In conclusion, the induction of apoptosis a nd cell death is much more efficient with LPL nanoparticles than LCA molecules as well as good hepatocyte specificity in vitro and in vivo.
목차
1. Introduction
2. Experimental Section
Chemicals and reagents
Synthesis of LPL
NMR and FTIR
Physicochemical characterization of LPL nanoparticles
Cytotoxicity assay
Western blot analysis
Apoptosis detection by Annexin V-FITC analysis
Ligand specificity of LPL in vivo
Statistical analyses
3. Results and Discussion
3.1. Preparation and characterization of LPL and PL
3.2. Stability of LPL and PL nanoparticles
3.2. Toxicity of LPL and PL nanoparticles
3.3. Ligand specificity of LPL with liver cells in vivo
3.4. Mechanism of apoptosis induced by LPL nanoparticles
4. Conclusions