PMID- 30019396 OWN - NLM STAT- MEDLINE DCOM- 20191108 LR - 20191108 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 7 IP - 17 DP - 2018 Sep TI - Nanocatalyst Complex Can Dephosphorylate Key Proteins in MAPK Pathway for Cancer Therapy. PG - e1800533 LID - 10.1002/adhm.201800533 [doi] AB - Controlling phosphorylation processes of proteins is a facile way for manipulating cell fates. Herein, a synergistic therapeutic strategy utilizing a near-infrared (NIR)-responsive nanocatalyst (NC) complex is presented, which is comprised of photoactive NC and protein phosphatase 2A (PP2A), to synergistically inhibit hyperphosphorylation of mitogen-activated protein kinase (MAPK) pathway for cancer therapy, as an example of many biological processes this approach can apply to. NIR-triggered release of PP2A specially dephosphorylates and inactivates mitogen-activated protein kinase kinase (MAP2K, also known as MEK) and extracellular regulated protein kinases (ERK) in the MAPK pathway, meanwhile, the NIR-triggered activation of NC decreases the level of intracellular adenosine triphosphate to attenuate protein phosphorylation of MEK and ERK. The synergistic therapeutics effectively suppress melanoma progression by inhibiting hyperphosphorylation of the MAPK pathway. In addition, the nanocatalyst complex reduces the risk of drug-resistance through inhibiting a rebound of RAS-GTP. The NIR-responsive nanocatalyst complex paves a novel way for cancer therapeutics. CI - (c) 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Tang, Rongbing AU - Tang R AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. AD - Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. AD - The University of Chinese Academy of Sciences, 19 A Yuquan Road, Shijingshan District, Beijing, 100049, P. R. China. FAU - Jia, Yuexiao AU - Jia Y AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. AD - The University of Chinese Academy of Sciences, 19 A Yuquan Road, Shijingshan District, Beijing, 100049, P. R. China. FAU - Zheng, Wenshu AU - Zheng W AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. AD - Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. AD - The University of Chinese Academy of Sciences, 19 A Yuquan Road, Shijingshan District, Beijing, 100049, P. R. China. FAU - Feng, Qiang AU - Feng Q AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. AD - The University of Chinese Academy of Sciences, 19 A Yuquan Road, Shijingshan District, Beijing, 100049, P. R. China. FAU - Zheng, Wenfu AU - Zheng W AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. FAU - Jiang, Xingyu AU - Jiang X AUID- ORCID: 0000-0002-5008-4703 AD - Beijing Engineering Research Center for BioNanotechnology and CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for NanoScience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing, 100190, P. R. China. AD - The University of Chinese Academy of Sciences, 19 A Yuquan Road, Shijingshan District, Beijing, 100049, P. R. China. LA - eng GR - 2013YQ190467/Ministry of Science and Technology of China/International GR - 81361140345/National Natural Science Foundation of China/International GR - 21535001/National Natural Science Foundation of China/International GR - 81730051/National Natural Science Foundation of China/International GR - 21761142006/National Natural Science Foundation of China/International GR - 31470911/National Natural Science Foundation of China/International GR - 81673039/National Natural Science Foundation of China/International GR - XDA09030305/Chinese Academy of Sciences/International GR - XDA09030307/Chinese Academy of Sciences/International GR - 121D11KYSB20170026/Chinese Academy of Sciences/International GR - CAS/SAFEA International Partnership Program for Creative Research/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180717 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Humans MH - Lysosomes/metabolism MH - Mitogen-Activated Protein Kinases/*metabolism MH - Neoplasms/drug therapy/metabolism MH - Phosphorylation/physiology MH - Signal Transduction/physiology OTO - NOTNLM OT - cancer therapy OT - dephosphorylation OT - drug delivery OT - nanoparticles EDAT- 2018/07/19 06:00 MHDA- 2019/11/09 06:00 CRDT- 2018/07/19 06:00 PHST- 2018/05/15 00:00 [received] PHST- 2018/06/18 00:00 [revised] PHST- 2018/07/19 06:00 [pubmed] PHST- 2019/11/09 06:00 [medline] PHST- 2018/07/19 06:00 [entrez] AID - 10.1002/adhm.201800533 [doi] PST - ppublish SO - Adv Healthc Mater. 2018 Sep;7(17):e1800533. doi: 10.1002/adhm.201800533. Epub 2018 Jul 17.