The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

Ji yun Huang; Ying mei Lu; Huan Wang; Jun Liu; Mei hua Liao; Ling juan Hong; Rong rong Tao; Muhammad Masood Ahmed; Ping Liu; Shuang shuang Liu; Kohji Fukunaga; Yong zhong Du; Feng Han

doi:10.1016/j.biomaterials.2013.07.009

The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

Ji yun Huang, Ying mei Lu, Huan Wang, Jun Liu, Mei hua Liao, Ling juan Hong, Rong rong Tao, Muhammad Masood Ahmed, Ping Liu, Shuang shuang Liu, Kohji Fukunaga, Yong zhong Du, Feng Han

PHA - Life and Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

Abstract

Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1^GFP/+ mice. Invivo study with two-photon confocal microscopy revealed abnormal Ca²⁺ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X₇^-/- mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X₇/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X₇-dependent neuroinflammatory response.

Original language	English
Pages (from-to)	7960-7970
Number of pages	11
Journal	Biomaterials
Volume	34
Issue number	32
DOIs	https://doi.org/10.1016/j.biomaterials.2013.07.009
Publication status	Published - 2013 Oct

Keywords

Brain
Lipid nanoparticles
Microglia
Neuroinflammatory response
P2X receptor
PEGylation

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2013.07.009

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@article{2b84462891e847279e371222192cdca6,

title = "The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain",

abstract = "Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1GFP/+ mice. Invivo study with two-photon confocal microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X7-/- mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X7/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X7-dependent neuroinflammatory response.",

keywords = "Brain, Lipid nanoparticles, Microglia, Neuroinflammatory response, P2X receptor, PEGylation",

author = "Huang, {Ji yun} and Lu, {Ying mei} and Huan Wang and Jun Liu and Liao, {Mei hua} and Hong, {Ling juan} and Tao, {Rong rong} and Ahmed, {Muhammad Masood} and Ping Liu and Liu, {Shuang shuang} and Kohji Fukunaga and Du, {Yong zhong} and Feng Han",

note = "Funding Information: This work was supported in part by National Natural Science Foundations of China ( 81120108023 , 91232705 , 81202533 ); National Basic Research Program of China (973 Program, 2009CB930300 ); The Science and Technology Planning Project of Zhejiang Province ( 2012F82G2010024 ). ",

year = "2013",

month = oct,

doi = "10.1016/j.biomaterials.2013.07.009",

language = "English",

volume = "34",

pages = "7960--7970",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "32",

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TY - JOUR

T1 - The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

AU - Huang, Ji yun

AU - Lu, Ying mei

AU - Wang, Huan

AU - Liu, Jun

AU - Liao, Mei hua

AU - Hong, Ling juan

AU - Tao, Rong rong

AU - Ahmed, Muhammad Masood

AU - Liu, Ping

AU - Liu, Shuang shuang

AU - Fukunaga, Kohji

AU - Du, Yong zhong

AU - Han, Feng

N1 - Funding Information: This work was supported in part by National Natural Science Foundations of China ( 81120108023 , 91232705 , 81202533 ); National Basic Research Program of China (973 Program, 2009CB930300 ); The Science and Technology Planning Project of Zhejiang Province ( 2012F82G2010024 ).

PY - 2013/10

Y1 - 2013/10

N2 - Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1GFP/+ mice. Invivo study with two-photon confocal microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X7-/- mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X7/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X7-dependent neuroinflammatory response.

AB - Nanocarrier-based drug delivery systems have attracted wide interest for the treatment of brain disease. However, neurotoxicity of nanoparticle has limited their therapeutic application. Here we demonstrated that lipid nanoparticles (LNs) accumulated in the brain parenchyma within 3h of intravenous injection to mice and persisted for more than 24 weeks, coinciding with a dramatic activation of brain microglia. Morphological characteristic of microglial activation also observed in LNs-treated Cx3cr1GFP/+ mice. Invivo study with two-photon confocal microscopy revealed abnormal Ca2+ waves in microglia following LNs injection. The correlated activation of caspase-1, IL-1β and neurovascular damage following LNs injection was attenuated in P2X7-/- mice. PEGylation of LNs reduced correlated nanoparticles aggregation. Moreover, PEGylation of LNs ameliorated the P2X7/caspase-1/IL-1β signalling-dependent microglia activation and neurovascular damage. In conclusion, PEGylation of LNs is a promising biomaterial for brain-targeted therapy that inhibits P2X7-dependent neuroinflammatory response.

KW - Brain

KW - Lipid nanoparticles

KW - Microglia

KW - Neuroinflammatory response

KW - P2X receptor

KW - PEGylation

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JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

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ER -

The effect of lipid nanoparticle PEGylation on neuroinflammatory response in mouse brain

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ASJC Scopus subject areas

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