標題: 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
作者: Hsieh, Tsung-Ying
Huang, Wei-Chen
Kang, Yi-Da
Chu, Chao-Yi
Liao, Wen-Lin
Chen, You-Yin
Chen, San-Yuan
材料科學與工程學系
Department of Materials Science and Engineering
關鍵字: central nervous system;gene transfection;graphene oxide;laser photothermal treatment;nanoparticles
公開日期: 十二月-2016
摘要: 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.
URI: http://dx.doi.org/10.1002/adhm.201600647
http://hdl.handle.net/11536/132753
ISSN: 2192-2640
DOI: 10.1002/adhm.201600647
期刊: ADVANCED HEALTHCARE MATERIALS
Volume: 5
Issue: 23
起始頁: 3016
結束頁: 3026
顯示於類別:期刊論文