PMID- 30223141
OWN - NLM
STAT- MEDLINE
DCOM- 20191014
LR  - 20191014
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 185
DP  - 2018 Dec
TI  - COX-2 Inhibition mediated anti-angiogenic activatable prodrug potentiates cancer 
      therapy in preclinical models.
PG  - 63-72
LID - S0142-9612(18)30637-9 [pii]
LID - 10.1016/j.biomaterials.2018.09.006 [doi]
AB  - Anti-angiogenesis, i.e., blocking the angiogenic pathway, has been considered as 
      an important component in current cancer therapeutic modalities. However, the 
      associated benefits have proven to be modest as tumor angiogenesis and regrowth 
      persist, probably due to other ill-defined complex angiogenic mechanisms. Herein, 
      we developed an indomethacin (IMC) incorporating system to mediate hypoxia 
      responsive prodrug (TA) and diagnostic agent (DA) in cancer theranostic 
      applications. Cyclooxygenase 2 (COX-2) elevated expression in several cancer 
      types is closely associated with severe tumor supporting vascularization factors. 
      Our strategy utilizing COX-2 inhibition augmented the anti-angiogenetic induced 
      hypoxia responsive prodrug activation well. Both in vitro and in vivo results 
      proved that DA and TA exhibited specificity towards COX-2 positive (+ve) HeLa and 
      A549 cancer cell lines and activation under hypoxic conditions. Compared with 
      controls (R1, and anticancer drug SN-38), TA displayed prolonged tumor retention 
      and enhanced therapeutic efficacy in xenograft mouse models at a reduced dosage. 
      Our results significantly highlighted the importance of COX-2 blockade mediated 
      anti-angiogenesis in complementing the hypoxia-responsive drug delivery systems 
      (DDSs) and could to beneficial for the rapid development of more efficacious 
      antitumor therapeutics.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Kim, Hyeong Seok
AU  - Kim HS
AD  - Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea.
FAU - Sharma, Amit
AU  - Sharma A
AD  - Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea.
FAU - Ren, Wen Xiu
AU  - Ren WX
AD  - Department of Radiology, The Affiliated Hospital of Southwest Medical University, 
      Luzhou, 646000, Sichuan Province, PR China; Department of Chemistry, Korea 
      University, Seoul, 02841, Republic of Korea. Electronic address: 
      xrenwenxiux@hotmail.com.
FAU - Han, Jiyou
AU  - Han J
AD  - Department of Biological Sciences, Laboratory of Stem Cell Research and 
      Biotechnology, Hyupsung University, Hwasung-si, 18330, Republic of Korea. 
      Electronic address: hanjiyou12@hanmail.net.
FAU - Kim, Jong Seung
AU  - Kim JS
AD  - Department of Chemistry, Korea University, Seoul, 02841, Republic of Korea. 
      Electronic address: jongskim@korea.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180910
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Prodrugs)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - A549 Cells
MH  - Angiogenesis Inhibitors/*administration & dosage/therapeutic use
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 2/metabolism
MH  - Cyclooxygenase 2 Inhibitors/*administration & dosage/therapeutic use
MH  - Drug Delivery Systems
MH  - HeLa Cells
MH  - Humans
MH  - Indomethacin/*administration & dosage/therapeutic use
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Neovascularization, Pathologic/drug therapy/metabolism/pathology
MH  - Prodrugs/*administration & dosage/therapeutic use
MH  - Theranostic Nanomedicine
MH  - Tumor Hypoxia/drug effects
OTO - NOTNLM
OT  - Anti-angiogenesis
OT  - COX-2
OT  - Cancer therapy
OT  - Hypoxia
OT  - Indomethacin
EDAT- 2018/09/18 06:00
MHDA- 2019/10/15 06:00
CRDT- 2018/09/18 06:00
PHST- 2018/06/27 00:00 [received]
PHST- 2018/08/26 00:00 [revised]
PHST- 2018/09/06 00:00 [accepted]
PHST- 2018/09/18 06:00 [pubmed]
PHST- 2019/10/15 06:00 [medline]
PHST- 2018/09/18 06:00 [entrez]
AID - S0142-9612(18)30637-9 [pii]
AID - 10.1016/j.biomaterials.2018.09.006 [doi]
PST - ppublish
SO  - Biomaterials. 2018 Dec;185:63-72. doi: 10.1016/j.biomaterials.2018.09.006. Epub 
      2018 Sep 10.