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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
Author(s) -
Hsieh TsungYing,
Huang WeiChen,
Kang YiDa,
Chu ChaoYi,
Liao WenLin,
Chen YouYin,
Chen SanYuan
Publication year - 2016
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201600647
Subject(s) - transfection , in vivo , photothermal therapy , genetic enhancement , polyethylenimine , gene delivery , in vitro , biophysics , materials science , microbiology and biotechnology , cell culture , chemistry , biology , nanotechnology , biochemistry , gene , genetics
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.