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Article: Luminescent cyclometalated platinum(II) complexes containing N-heterocyclic carbene ligands with potent in vitro and in vivo anti-cancer properties accumulate in cytoplasmic structures of cancer cells

TitleLuminescent cyclometalated platinum(II) complexes containing N-heterocyclic carbene ligands with potent in vitro and in vivo anti-cancer properties accumulate in cytoplasmic structures of cancer cells
Authors
KeywordsAnti-cancer agents
Anticancer drug
Apoptosis
Biological activities
Biological reductions
Issue Date2011
PublisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp
Citation
Chemical Science, 2011, v. 2 n. 4, p. 728-736 How to Cite?
Abstract
Contrary to most platinum-based anti-cancer agents which target DNA, coordination of N-heterocyclic carbene (NHC) ligands to cyclometalated platinum(II) complexes confers these luminescent complexes to other cellular target(s). The strong Pt-Ccarbene bond(s) renders the platinum(II) complexes to display unique photophysical properties and enhanced stability against biological reduction and ligand exchange reactions. The platinum complexes described in this work are highly cytotoxic and display high specificity to cancerous cells. Among them, [(C^N^N)PtII(N,N'-nBu2NHC)]PF6 (1a, where HC^N^N = 6-phenyl-2,2'-bipyridine) with a lipophilic carbon chain on the carbene ligand induces apoptosis in cancer cells, demonstrates an enhancing synergistic effect with cisplatin in vitro, and displays potent in vivo activities using nude mice models. As this complex is strongly emissive, its cellular localization can be traced using emission microscopy. In contrast to common platinum-based anti-cancer agents, 1a does not accumulate in the vicinity of DNA but preferentially accumulates in cytoplasmic structures including sites where active survivin, an inhibitor of apoptosis (IAP), is located. In vitro, 1a significantly inhibits the expression of survivin, activates poly(ADP-ribose) polymerase (PARP) and induces apoptosis in cancer cells. Given the ease of structural modification of NHC ligand to alter the overall biological activities, these [(C^N^N)PtII(NHC)]+ complexes having unique photophysical properties provide an entry to a new class of potential anti-cancer drug leads. © The Royal Society of Chemistry 2011.
Persistent Identifierhttp://hdl.handle.net/10722/134374
ISSN
2013 Impact Factor: 8.601
ISI Accession Number ID
Funding AgencyGrant Number
ITF-Tier 2 projectITS/134/09FP
Areas of Excellence ProgramAoE/P-10/01
Funding Information:

We acknowledge support from the ITF-Tier 2 project (ITS/134/09FP) administrated by Innovation and Technology Commission (HKSAR, China), and the Areas of Excellence Program (AoE/P-10/01) administrated by University Grants Council (HKSAR, China). We thank Drs J.-S. Huang and C.-N. Lok for their helpful discussion to this project.

References
Grants

 

Author Affiliations
  1. Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong
DC FieldValueLanguage
dc.contributor.authorSun, RWYen_HK
dc.contributor.authorChow, ALFen_HK
dc.contributor.authorLi, XHen_HK
dc.contributor.authorYan, JJen_HK
dc.contributor.authorChui, SSYen_HK
dc.contributor.authorChe, CMen_HK
dc.date.accessioned2011-06-17T09:18:45Z-
dc.date.available2011-06-17T09:18:45Z-
dc.date.issued2011en_HK
dc.identifier.citationChemical Science, 2011, v. 2 n. 4, p. 728-736en_HK
dc.identifier.issn2041-6520en_HK
dc.identifier.urihttp://hdl.handle.net/10722/134374-
dc.description.abstractContrary to most platinum-based anti-cancer agents which target DNA, coordination of N-heterocyclic carbene (NHC) ligands to cyclometalated platinum(II) complexes confers these luminescent complexes to other cellular target(s). The strong Pt-Ccarbene bond(s) renders the platinum(II) complexes to display unique photophysical properties and enhanced stability against biological reduction and ligand exchange reactions. The platinum complexes described in this work are highly cytotoxic and display high specificity to cancerous cells. Among them, [(C^N^N)PtII(N,N'-nBu2NHC)]PF6 (1a, where HC^N^N = 6-phenyl-2,2'-bipyridine) with a lipophilic carbon chain on the carbene ligand induces apoptosis in cancer cells, demonstrates an enhancing synergistic effect with cisplatin in vitro, and displays potent in vivo activities using nude mice models. As this complex is strongly emissive, its cellular localization can be traced using emission microscopy. In contrast to common platinum-based anti-cancer agents, 1a does not accumulate in the vicinity of DNA but preferentially accumulates in cytoplasmic structures including sites where active survivin, an inhibitor of apoptosis (IAP), is located. In vitro, 1a significantly inhibits the expression of survivin, activates poly(ADP-ribose) polymerase (PARP) and induces apoptosis in cancer cells. Given the ease of structural modification of NHC ligand to alter the overall biological activities, these [(C^N^N)PtII(NHC)]+ complexes having unique photophysical properties provide an entry to a new class of potential anti-cancer drug leads. © The Royal Society of Chemistry 2011.en_HK
dc.languageengen_US
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.aspen_HK
dc.relation.ispartofChemical Scienceen_HK
dc.subjectAnti-cancer agents-
dc.subjectAnticancer drug-
dc.subjectApoptosis-
dc.subjectBiological activities-
dc.subjectBiological reductions-
dc.titleLuminescent cyclometalated platinum(II) complexes containing N-heterocyclic carbene ligands with potent in vitro and in vivo anti-cancer properties accumulate in cytoplasmic structures of cancer cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=2041-6520&volume=2&issue=4&spage=728&epage=736&date=2011&atitle=Luminescent+cyclometalated+platinum(II)+complexes+containing+N-heterocyclic+carbene+ligands+with+potent+in+vitro+and+in+vivo+anti-cancer+properties+accumulate+in+cytoplasmic+structures+of+cancer+cells-
dc.identifier.emailSun, RWY: rwysun@hku.hken_HK
dc.identifier.emailChui, SSY: chuissy@hkucc.hku.hken_HK
dc.identifier.emailChe, CM: cmche@hku.hken_HK
dc.identifier.authoritySun, RWY=rp00781en_HK
dc.identifier.authorityChui, SSY=rp00686en_HK
dc.identifier.authorityChe, CM=rp00670en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1039/c0sc00593ben_HK
dc.identifier.scopuseid_2-s2.0-79955572736en_HK
dc.identifier.hkuros185812en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79955572736&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume2en_HK
dc.identifier.issue4en_HK
dc.identifier.spage728en_HK
dc.identifier.epage736en_HK
dc.identifier.eissn2041-6539-
dc.identifier.isiWOS:000288387600022-
dc.publisher.placeUnited Kingdomen_HK
dc.relation.projectDiscovery and Pre-Clinical Evaluation of Promising Metal-Based Anti-Cancer Drug Leads-
dc.relation.projectInstitute of molecular technology for drug discovery and synthesis-
dc.identifier.scopusauthoridSun, RWY=26325835800en_HK
dc.identifier.scopusauthoridChow, ALF=36463401100en_HK
dc.identifier.scopusauthoridLi, XH=36012409200en_HK
dc.identifier.scopusauthoridYan, JJ=35752634300en_HK
dc.identifier.scopusauthoridChui, SSY=8297453100en_HK
dc.identifier.scopusauthoridChe, CM=7102442791en_HK

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