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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
发表期刊JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
ISSN0002-7863
卷号140期号:11页码:4164-4171
摘要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.
文章类型Article
WOS标题词Science & Technology ; Physical Sciences
DOI10.1021/jacs.8b01641
收录类别SCI
语种英语
关键词[WOS]NEURAL STEM-CELLS ; SMALL INTERFERING RNA ; NUCLEAR RECEPTOR TLX ; STEM/PROGENITOR CELLS ; SELF-RENEWAL ; CO-DELIVERY ; BDNF ; CANCER ; BRAIN ; NANOPARTICLES
WOS研究方向Chemistry
WOS类目Chemistry, Multidisciplinary
项目资助者National 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) ; "Strategic Priority Research Program" of the Chinese Academy of Sciences(XDA09030301-3) ; 51373177 ; 51573188)
WOS记录号WOS:000428356000048
引用统计
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/24162
专题生化工程国家重点实验室
作者单位1.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
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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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