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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
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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
 
AuthorsSun, RWY1
Chow, ALF1
Li, XH1
Yan, JJ1
Chui, SSY1
Che, CM1
 
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
 
CitationChemical Science, 2011, v. 2 n. 4, p. 728-736 [How to Cite?]
DOI: http://dx.doi.org/10.1039/c0sc00593b
 
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.
 
ISSN2041-6520
2012 Impact Factor: 8.314
 
DOIhttp://dx.doi.org/10.1039/c0sc00593b
 
ISI Accession Number IDWOS:000288387600022
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.

 
ReferencesReferences in Scopus
 
GrantsDiscovery and Pre-Clinical Evaluation of Promising Metal-Based Anti-Cancer Drug Leads
Institute of molecular technology for drug discovery and synthesis
 
DC FieldValue
dc.contributor.authorSun, RWY
 
dc.contributor.authorChow, ALF
 
dc.contributor.authorLi, XH
 
dc.contributor.authorYan, JJ
 
dc.contributor.authorChui, SSY
 
dc.contributor.authorChe, CM
 
dc.date.accessioned2011-06-17T09:18:45Z
 
dc.date.available2011-06-17T09:18:45Z
 
dc.date.issued2011
 
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.
 
dc.description.natureLink_to_subscribed_fulltext
 
dc.identifier.citationChemical Science, 2011, v. 2 n. 4, p. 728-736 [How to Cite?]
DOI: http://dx.doi.org/10.1039/c0sc00593b
 
dc.identifier.doihttp://dx.doi.org/10.1039/c0sc00593b
 
dc.identifier.eissn2041-6539
 
dc.identifier.epage736
 
dc.identifier.hkuros185812
 
dc.identifier.isiWOS:000288387600022
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.

 
dc.identifier.issn2041-6520
2012 Impact Factor: 8.314
 
dc.identifier.issue4
 
dc.identifier.openurl
 
dc.identifier.scopuseid_2-s2.0-79955572736
 
dc.identifier.spage728
 
dc.identifier.urihttp://hdl.handle.net/10722/134374
 
dc.identifier.volume2
 
dc.languageeng
 
dc.publisherRoyal Society of Chemistry. The Journal's web site is located at http://www.rsc.org/publishing/journals/sc/About.asp
 
dc.publisher.placeUnited Kingdom
 
dc.relation.ispartofChemical Science
 
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.relation.referencesReferences in Scopus
 
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 cells
 
dc.typeArticle
 
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Author Affiliations
  1. Institute of Molecular Technology for Drug Discovery and Synthesis, Hong Kong