Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma
| العنوان: | Galactose Derivative-Modified Nanoparticles for Efficient siRNA Delivery to Hepatocellular Carcinoma |
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| المؤلفون: | 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 |
| المصدر: | Biomacromolecules. 19:2330-2339 |
| بيانات النشر: | American Chemical Society (ACS), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1526-4602 1525-7797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c73ea5424d03a2f7397133165236a1deTest https://doi.org/10.1021/acs.biomac.8b00358Test |
| رقم الانضمام: | edsair.doi.dedup.....c73ea5424d03a2f7397133165236a1de |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15264602 15257797 |
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