Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma
| Autor: | Chia-Lung Tsai, Shao-Feng Huang, Yun-Chieh Sung, Sheng-Kai Wang, Kuan-Wei Huang, Guann-Jen Chern, Rui-Lin Huang, Yu-Tsung Lai, Cheng-Chin Chiang, Ting-Yun Shiue, Yunching Chen, Ting-Lun Ho, Pi-Bei Hwang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Small interfering RNA Carcinoma Hepatocellular Polymers and Plastics Aptamer Bioengineering Asialoglycoprotein Receptor 010402 general chemistry 01 natural sciences Biomaterials Mice 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems In vivo Tumor Microenvironment Materials Chemistry medicine Animals RNA Small Interfering Tumor microenvironment Liver Neoplasms Galactose medicine.disease Galactoside digestive system diseases In vitro Neoplasm Proteins 0104 chemical sciences 030104 developmental biology chemistry Cancer research Nanoparticles Asialoglycoprotein receptor Liver cancer |
| Zdroj: | Biomacromolecules. 19:2330-2339 |
| ISSN: | 1526-4602 1525-7797 |
| Popis: | Successful siRNA therapy requires suitable delivery systems with targeting moieties such as small molecules, peptides, antibodies, or aptamers. Galactose (Gal) residues recognized by the asialoglycoprotein receptor (ASGPR) can serve as potent targeting moieties for hepatocellular carcinoma (HCC) cells. However, efficient targeting to HCC via galactose moieties rather than normal liver tissues in HCC patients remains a challenge. To achieve more efficient siRNA delivery in HCC, we synthesized various galactoside derivatives and investigated the siRNA delivery capability of nanoparticles modified with those galactoside derivatives. In this study, we assembled lipid/calcium/phosphate nanoparticles (LCP NPs) conjugated with eight types of galactoside derivatives and demonstrated that phenyl β-d-galactoside-decorated LCP NPs (L4-LCP NPs) exhibited a superior siRNA delivery into HCC cells compared to normal hepatocytes. VEGF siRNAs delivered by L4-LCP NPs downregulated VEGF expression in HCC in vitro and in vivo and led to a potent antiangiogenic effect in the tumor microenvironment of a murine orthotopic HCC model. The efficient delivery of VEGF siRNA by L4-LCP NPs that resulted in significant tumor regression indicates that phenyl galactoside could be a promising HCC-targeting ligand for therapeutic siRNA delivery to treat liver cancer. |
| Databáze: | OpenAIRE |
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