Neurotensin-Conjugated Reduced Graphene Oxide with Multi-Stage Near-Infrared-Triggered Synergic Targeted Neuron Gene Transfection In Vitro and In Vivo for Neurodegenerative Disease Therapy
| Autor: | Chao Yi Chu, Wen Lin Liao, You Yin Chen, Wei-Chen Huang, Tsung Ying Hsieh, Yi Da Kang, San-Yuan Chen |
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| Rok vydání: | 2016 |
| Předmět: |
Cell Membrane Permeability
Materials science Genetic enhancement Cell Biomedical Engineering Pharmaceutical Science 02 engineering and technology Transfection 010402 general chemistry 01 natural sciences Biomaterials Cell membrane Mice chemistry.chemical_compound In vivo Cell Line Tumor medicine Animals Polyethyleneimine Neurotensin Neurons Polyethylenimine Spectroscopy Near-Infrared Gene Transfer Techniques Neurodegenerative Diseases Oxides Genetic Therapy Photothermal therapy 021001 nanoscience & nanotechnology Molecular biology In vitro Rats 0104 chemical sciences Mice Inbred C57BL medicine.anatomical_structure chemistry Biophysics Nanoparticles Graphite 0210 nano-technology Plasmids |
| Zdroj: | Advanced Healthcare Materials. 5:3016-3026 |
| ISSN: | 2192-2640 |
| Popis: | Delivery efficiency with gene transfection is a pivotal point in achieving maximized therapeutic efficacy and has been an important challenge with central nervous system (CNS) diseases. In this study, neurotensin (NT, a neuro-specific peptide)-conjugated polyethylenimine (PEI)-modified reduced graphene oxide (rGO) nanoparticles with precisely controlled two-stage near-infrared (NIR)-laser photothermal treatment to enhance the ability to target neurons and achieve high gene transfection in neurons. First-stage NIR laser irradiation on the cells with nanoparticles attached on the surface can increase the permeability of the cell membrane, resulting in an apparent increase in cellular uptake compared to untreated cells. In addition, second-stage NIR laser irradiation on the cells with nanoparticles inside can further induce endo/lysosomal cavitation, which not only helps nanoparticles escape from endo/lysosomes but also prevents plasmid DNA (pDNA) from being digested by DNase I. At least double pDNA amount can be released from rGO-PEI-NT/pDNA under NIR laser trigger release compared to natural release. Moreover, in vitro differentiated PC-12 cell and in vivo mice (C57BL/6) brain transfection experiments have demonstrated the highest transfection efficiency occurring when NT modification is combined with external multi-stage stimuli-responsive NIR laser treatment. The combination of neuro-specific targeting peptide and external NIR-laser-triggered aid provides a nanoplatform for gene therapy in CNS diseases. |
| Databáze: | OpenAIRE |
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