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

Tsung Ying Hsieh, Wei Chen Huang, Yi Da Kang, Chao Yi Chu, Wen Lin Liao, You Yin Chen, San Yuan Chen

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3016-3026
Number of pages11
JournalAdvanced healthcare materials
Volume5
Issue number23
DOIs
Publication statusPublished - Dec 7 2016
Externally publishedYes

Fingerprint

Neurodegenerative diseases
Neurotensin
Graphite
Infrared lasers
Neurodegenerative Diseases
Oxides
Graphene
Neurons
Transfection
Lasers
Genes
Infrared radiation
Nanoparticles
Polyethyleneimine
Plasmids
DNA
Central Nervous System Diseases
Neurology
Laser beam effects
Peptides

Keywords

  • central nervous system
  • gene transfection
  • graphene oxide
  • laser photothermal treatment
  • nanoparticles

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering
  • Pharmaceutical Science

Cite this

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. / Hsieh, Tsung Ying; Huang, Wei Chen; Kang, Yi Da; Chu, Chao Yi; Liao, Wen Lin; Chen, You Yin; Chen, San Yuan.

In: Advanced healthcare materials, Vol. 5, No. 23, 07.12.2016, p. 3016-3026.

Research output: Contribution to journalArticle

@article{1138942ce3e04462aef8ffa31ef8dd97,
title = "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",
abstract = "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.",
keywords = "central nervous system, gene transfection, graphene oxide, laser photothermal treatment, nanoparticles",
author = "Hsieh, {Tsung Ying} and Huang, {Wei Chen} and Kang, {Yi Da} and Chu, {Chao Yi} and Liao, {Wen Lin} and Chen, {You Yin} and Chen, {San Yuan}",
year = "2016",
month = "12",
day = "7",
doi = "10.1002/adhm.201600647",
language = "English",
volume = "5",
pages = "3016--3026",
journal = "Advanced healthcare materials",
issn = "2192-2640",
publisher = "John Wiley and Sons Ltd",
number = "23",

}

TY - JOUR

T1 - 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

AU - Hsieh, Tsung Ying

AU - Huang, Wei Chen

AU - Kang, Yi Da

AU - Chu, Chao Yi

AU - Liao, Wen Lin

AU - Chen, You Yin

AU - Chen, San Yuan

PY - 2016/12/7

Y1 - 2016/12/7

N2 - 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.

AB - 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.

KW - central nervous system

KW - gene transfection

KW - graphene oxide

KW - laser photothermal treatment

KW - nanoparticles

UR - http://www.scopus.com/inward/record.url?scp=84995897816&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995897816&partnerID=8YFLogxK

U2 - 10.1002/adhm.201600647

DO - 10.1002/adhm.201600647

M3 - Article

AN - SCOPUS:84995897816

VL - 5

SP - 3016

EP - 3026

JO - Advanced healthcare materials

JF - Advanced healthcare materials

SN - 2192-2640

IS - 23

ER -