CAS OpenIR
Isothermal kinase-triggered supramolecular assemblies as drug sensitizers
Liu, Dongdong1,2; Miao, Zhe1; Wu, Chengling1; He, Fangfei1; Ren, Peng3; Bai, Shuo3; Jiang, Xingyu1,2,4; Gao, Yuan1,2
2020-01-28
Source PublicationCHEMICAL SCIENCE
ISSN2041-6520
Volume11Issue:4Pages:1132-1139
AbstractProtein kinases, the main regulators of a vast map of cellular processes, are the most attractive targets in drug discovery. Despite a few successful examples of protein kinase inhibitors, the drug discovery strategy of downregulating protein kinase activity has been quite limited and often fails even in animal models. Here, we utilize protein kinase A (PKA) activity to design PKA-triggered supramolecular assemblies with anticancer activities. Grafting a suitable peptide to PNIPAM raises the critical temperature of the LCST polymer above body temperature. Interestingly, the corresponding phosphorylated polymer has a critical temperature below body temperature, making this peptide-appended PNIPAM a suitable polymer for the PKA-triggered supramolecular assembly process. PKA-triggered assembly occurs selectively in PKA-upregulated MCF-7 cells, which disturbs the cytoskeleton and sensitizes cancer cells against doxorubicin. The chemosensitization is also observed in vivo to identify effective tumor inhibitors with satisfactory biocompatibility. Overall, this phosphorylation-induced (in principle, PKA-catalyzed) supramolecular assembly opens up a promising chemotherapy strategy for combating kinase-upregulated cancer.
DOI10.1039/c9sc04317a
Language英语
WOS KeywordCANCER-CELLS ; PROTEIN ; MEMBRANE ; INHIBITORS ; INDUCE
Funding ProjectNational Key R&D Program of China[2017YFA0205901] ; NSFC[21675036] ; NSFC[51873046] ; NSFC[21705029] ; NSKF[201818] ; Hundred Talents Project of the Chinese Academy of Sciences
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
Funding OrganizationNational Key R&D Program of China ; NSFC ; NSKF ; Hundred Talents Project of the Chinese Academy of Sciences
WOS IDWOS:000510929600022
PublisherROYAL SOC CHEMISTRY
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ipe.ac.cn/handle/122111/39274
Collection中国科学院过程工程研究所
Corresponding AuthorGao, Yuan
Affiliation1.Natl Ctr Nanosci & Technol, CAS Key Lab Biomed Effects Nanomat & Nanosafety, CAS Ctr Excellence Nanosci, Beijing 100190, Peoples R China
2.Univ Chinese Acad Sci, Sino Danish Coll, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Inst Proc Engn, Beijing 100190, Peoples R China
4.Southern Univ Sci & Technol, Dept Biomed Engn, Shenzhen 518055, Guangdong, Peoples R China
Recommended Citation
GB/T 7714
Liu, Dongdong,Miao, Zhe,Wu, Chengling,et al. Isothermal kinase-triggered supramolecular assemblies as drug sensitizers[J]. CHEMICAL SCIENCE,2020,11(4):1132-1139.
APA Liu, Dongdong.,Miao, Zhe.,Wu, Chengling.,He, Fangfei.,Ren, Peng.,...&Gao, Yuan.(2020).Isothermal kinase-triggered supramolecular assemblies as drug sensitizers.CHEMICAL SCIENCE,11(4),1132-1139.
MLA Liu, Dongdong,et al."Isothermal kinase-triggered supramolecular assemblies as drug sensitizers".CHEMICAL SCIENCE 11.4(2020):1132-1139.
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