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Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect
Wu,Chun1; Wu,Ke Jia2; Liu,Jin Biao1,3; Wang,Wanhe1; Leung,Chung Hang2; Ma,Dik Lung1
Source PublicationChemical Science

Dual-functional theranostics are powerful tools that can allow for the in-field understanding of cancer pathology, yet their use is held back by the paucity of suitable theranostics for living systems. Moreover, typical in vitro screening conditions for probe molecules do not necessarily generate candidates that can function effectively in the natural in cellulo environment, limiting their follow-up use in living systems. We introduce herein a general strategy for the development of an iridium(iii) theranostic by grafting a well-known inhibitor as a "binding unit"onto an iridium(iii) complex precursor as a "signaling unit". To further optimize their emissive properties, we explored the effect of imaging behavior by incorporating different substituents onto the parental "signaling unit". This design concept was validated by a series of tailored iridium(iii) theranostics 2a-2h for the visualization and inhibition of EGFR in living cancer cells. By comprehensively assessing the theranostic potency of 2a-2h in both in vitro and in cellulo contexts, probe 2f containing electron-donating methoxy groups on the "signaling unit"was discovered to be the most promising candidate theranostic with desirable photophysical/chemical properties. Probe 2f selectively bound to EGFR in vitro and in cellulo, enabling it to selectively discriminate living EGFR-overexpressing cancer cells from normal cells that express low levels of EGFR with an "always-on"luminescence signal output. In particular, its long-lived lifetime enabled its luminescence signal to be readily distinguished from the interfering fluorescence of organic dyes by using time-resolved techniques. Complex 2f simultaneously visualized and inhibited EGFR in a dose-dependent manner, leading to a reduction in the phosphorylation of downstream proteins ERK and MEK, and inhibition of the activity of downstream transcription factor AP1. Notably, complex 2f is comparable to the parental EGFR inhibitor 1b, in terms of both inhibitory activity against EGFR and cytotoxicity against EGFR-overexpressing cancer cells. This tailored dual-functional iridium(iii) theranostic toolkit provides an alternative strategy for the personalized diagnosis and treatment of cancers.

URLView the original
Indexed BySCIE
WOS Research AreaChemistry
WOS SubjectChemistry, Multidisciplinary
WOS IDWOS:000589505900027
Scopus ID2-s2.0-85096346510
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Cited Times [WOS]:6   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorLeung,Chung Hang; Ma,Dik Lung
Affiliation1.Department of Chemistry,Hong Kong Baptist University,Kowloon,999077,Hong Kong
2.Institute of Chinese Medical Sciences,State Key Laboratory of Quality Research in Chinese Medicine,University of Macau,Taipa,999078,Macao
3.School of Metallurgical and Chemical Engineering,Jiangxi University of Science and Technology,Ganzhou,China
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wu,Chun,Wu,Ke Jia,Liu,Jin Biao,et al. Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect[J]. Chemical Science,2020,11(42):11404-11412.
APA Wu,Chun,Wu,Ke Jia,Liu,Jin Biao,Wang,Wanhe,Leung,Chung Hang,&Ma,Dik Lung.(2020).Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect.Chemical Science,11(42),11404-11412.
MLA Wu,Chun,et al."Structure-guided discovery of a luminescent theranostic toolkit for living cancer cells and the imaging behavior effect".Chemical Science 11.42(2020):11404-11412.
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