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Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy
Li, Yan1; Li, Yanhui1; Ji, Weihong1,2; Lu, Zhiguo1,2; Liu, Linying1,2; Shi, Yuanjie1; Ma, Guanghui1; Zhang, Xin1
2018-03-21
Source PublicationJOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN0002-7863
Volume140Issue:11Pages:4164-4171
Abstract

Due to the vast differences in chemical properties among small molecule drugs, nucleotide drugs, and superparamagnetic iron oxide nanocubes (SPIONs), such as charge and hydrophobicity, entrapment of these within a single carrier for traceable synergistic therapy has been proven difficult. Herein, we synthesize positively charged polyprodrug amphiphiles. The hydrophobic polyprodrug unit of the amphiphiles is positively charged, which can simultaneously load hydrophobic SPIONs and absorb negative let-7b antisense oligonucleotide to construct traceable co-delivery nanoparticles (NPs). This characteristic avoids the use of inert materials and enhances drug loading of the traceable NPs. The traceable NPs can achieve controlled release of drugs to reduce the differentiation of exogenous neural stem cells (NSCs) and enhance their secretion of brain-derived neurotrophic factor (BDNF) synergistically. Exogenous NSCs treated with the NPs significantly rescue the memory deficits in 2xTg-AD mice. In addition, the transplantation site and migration of exogenous NSCs can be traced using the SPIONs with high r(2) value for magnetic resonance imaging. Therefore, traceable NPs self-assembled from the positively charged polyprodrug amphiphiles may have the potential to open up a new avenue for treatment of Alzheimer's disease (AD), as well as other neurodegenerative disorders.

SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
DOI10.1021/jacs.8b01641
Indexed BySCI
Language英语
WOS KeywordNeural Stem-cells ; Small Interfering Rna ; Nuclear Receptor Tlx ; Stem/progenitor Cells ; Self-renewal ; Co-delivery ; Bdnf ; Cancer ; Brain ; Nanoparticles
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
Funding OrganizationNational High Technology Research and Development Program(2016YFA0200303) ; National Natural Science Foundation of China(31522023 ; Beijing Natural Science Foundation(L172046) ; Beijing Municipal Science & Technology Commission(Z161100002616015)
WOS IDWOS:000428356000048
Citation statistics
Cited Times:21[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/24162
Collection生化工程国家重点实验室
Affiliation1.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Li, Yan,Li, Yanhui,Ji, Weihong,et al. Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2018,140(11):4164-4171.
APA Li, Yan.,Li, Yanhui.,Ji, Weihong.,Lu, Zhiguo.,Liu, Linying.,...&Zhang, Xin.(2018).Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,140(11),4164-4171.
MLA Li, Yan,et al."Positively Charged Polyprodrug Amphiphiles with Enhanced Drug Loading and Reactive Oxygen Species-Responsive Release Ability for Traceable Synergistic Therapy".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 140.11(2018):4164-4171.
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