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

10.1039/c9sc04317a

Chemical Science   影响因子和分区

2041-6520

2041-6539

Protein 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.

SCI ; EI

英语

NI期刊 ; NI论文

其他

[201818] ; [2017YFA0205901] ; National Natural Science Foundation of China[51873046]

Chemistry

Chemistry, Multidisciplinary

WOS:000510929600022

Royal Society of Chemistry

20200608127837

Azobenzene ; Biocompatibility ; Chemotherapy ; Diseases ; Peptides ; Phosphorylation ; Physiology ; Supramolecular chemistry ; Temperature

Bioengineering and Biology:461 ; Thermodynamics:641.1 ; Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Organic Compounds:804.1

2-s2.0-85078866235

Scopus

1.CAS Center for Excellence in Nanoscience,CAS Key Laboratory of Biomedical Effects of Nanomaterials and Nanosafety,National Center for Nanoscience and Technology,Beijing,100190,China
2.Sino-Danish College,University of Chinese Academy of Sciences,Beijing,100049,China
3.Institute of Process Engineering,Chinese Academy of Sciences,Beijing,100190,China
4.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen, Guangdong,518055,China

Liu，Dongdong,Miao，Zhe,Wu，Chengling,et al. Isothermal kinase-triggered supramolecular assemblies as drug sensitizers[J]. Chemical Science,2020,11(4):1132-1139.

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.

Liu，Dongdong,et al."Isothermal kinase-triggered supramolecular assemblies as drug sensitizers".Chemical Science 11.4(2020):1132-1139.