Chemical strategies to modify amyloidogenic peptides using iridium(<scp>iii</scp>) complexes: coordination and photo-induced oxidation

Kang, Juhye; Nam, Jung Seung; Lee, Hyuck Jin; Nam, Geewoo; Rhee, Hyun‐Woo; Kwon, Tae‐Hyuk; Lim, Mi Hee

doi:10.1039/c9sc00931k

Cited by 27 publications

(16 citation statements)

References 73 publications

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“…In general, the transition Ir(III) complexes has the ability to alter peptides due to its hydrolytic cleavage and oxidation. Hence, a single Ir(III) complex was used to modulate the Aβ peptides in Alzheimer's disease 103 . This Ir(III) complex greatly regulates the aggregation pathways of two main Aβ isoforms, Aβ 40 and Aβ 42 , as well as the production of toxic Aβ peptides.…”

Section: Antihypoxic Tumor Strategymentioning

confidence: 99%

Recent advances of transition Ir(III) complexes as photosensitizers for improved photodynamic therapy

Zhang

2021

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Photodynamic therapy (PDT), a minimally invasive procedure, usually required photosensitizer (PS) under light irradiation to convert the absorbed light energy into reactive oxygen species (ROS) to cause cancer cell apoptosis. The PSs with abundant excited triplet state play a critical role to guarantee the PDT effect. Transition Ir(III) complexes has been proved to be an effective PSs for PDT, owing to their high intersystem crossing (ISC) ability, tunable optical properties, long excited state lifetimes. However, poor biocompatibility, short excitation wavelength, and high oxygen dependence limit their biomedical applications. This review summarizes important progress of Ir(III) complexes as PS in improved PDT, including: (1) the strategy of nanoparticles is employed to improve their biocompatibility, and significantly enhance the cellular intracellular efficiency at the same time. (2) Their excitation wavelength is successfully extended by combining fluorophores, forming nanoscale Metal‐Organic frameworks (nMOFs) or two‐photon excited therapy. (3) Their therapeutic effect for antihypoxic tumors is enhanced by constructing mitochondrial‐targeted PS or type I PDT. In addition, simple modification of the precursor is beneficial to obtain a more excellent therapeutic effect. Finally, we brief summarize the current challenges and future research opportunities for Ir(III) complexes in this research field.

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Section: Antihypoxic Tumor Strategymentioning

confidence: 99%

Recent advances of transition Ir(III) complexes as photosensitizers for improved photodynamic therapy

Zhang

2021

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“…[ 32–37 ] Iridium (III) complexes have also been explored as an “off‐to‐on” chemosensor for biosensing and activatable imaging applications. [ 25,38 ] In addition to phosphorescence signaling, its long‐lived triplet state allows for the production of singlet oxygen, [ 39,40 ] thus suggesting its potential as an afterglow initiator capable of singlet oxygen ( 1 O 2 )‐mediated oxidation of afterglow substrate in the chemiluminescence mechanism. By virtue of such versatility, iridium complexes are considered as a promising candidate for constructing the multifunctional molecular framework.…”

Section: Introductionmentioning

confidence: 99%

Multifunction‐Harnessed Afterglow Nanosensor for Molecular Imaging of Acute Kidney Injury In Vivo

Anjong

Choi

Yoo

et al. 2022

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Afterglow is superior to other optical modalities for biomedical applications in that it can exclude the autofluorescence background. Nevertheless, afterglow has rarely been applied to the high‐contrast “off‐to‐on” activatable sensing scheme because the complicated afterglow systems hamper the additional inclusion of sensory functions while preserving the afterglow luminescence. Herein, a simple formulation of a multifunctional components‐incorporated afterglow nanosensor (MANS) is developed for the superoxide‐responsive activatable afterglow imaging of cisplatin‐induced kidney injury. A multifunctional iridium complex (Ir‐OTf) is designed to recover its photoactivities (phosphorescence and the ability of singlet oxygen‐generating afterglow initiator) upon exposure to superoxide. To construct the nanoscopic afterglow detection system (MANS), Ir‐OTf is incorporated with another multifunctional molecule (rubrene) in the polymeric micellar nanoparticle, where rubrene also plays dual roles as an afterglow substrate and a luminophore. The multiple functions covered by Ir‐OTf and rubrene renders the composition of MANS quite simple, which exhibits superoxide‐responsive “off‐to‐on” activatable afterglow luminescence for periods longer than 11 min after the termination of pre‐excitation. Finally, MANS is successfully applied to the molecular imaging of cisplatin‐induced kidney injury with activatable afterglow signals responsive to pathologically overproduced superoxide in a mouse model without autofluorescence background.

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“…Oxidative stress induced by photosensitisers causes chemical modifications of biomolecules including proteins 7 – 9 , unsaturated lipids 10 , 11 , and DNA 12 , 13 . Notably, protein modifications occurring via methionine oxidation and dityrosine crosslinking are clearly described chemical modifications for mitochondrial oxidation-induced cell death 9 , 14 . However, the connection between the chemical modifications of mitochondrial proteins and the biological response in cell death remains elusive due to the absence of a chemical tool to analyse the biological phenomena (i.e., environmental changes in mitochondrial surroundings in terms of viscosity, polarity, morphology, pH, and temperature) that occur in mitochondria in response to oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser

et al. 2021

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Mitochondrial oxidation-induced cell death, a physiological process triggered by various cancer therapeutics to induce oxidative stress on tumours, has been challenging to investigate owing to the difficulties in generating mitochondria-specific oxidative stress and monitoring mitochondrial responses simultaneously. Accordingly, to the best of our knowledge, the relationship between mitochondrial protein oxidation via oxidative stress and the subsequent cell death-related biological phenomena has not been defined. Here, we developed a multifunctional iridium(III) photosensitiser, Ir-OA, capable of inducing substantial mitochondrial oxidative stress and monitoring the corresponding change in viscosity, polarity, and morphology. Photoactivation of Ir-OA triggers chemical modifications in mitochondrial protein-crosslinking and oxidation (i.e., oxidative phosphorylation complexes and channel and translocase proteins), leading to microenvironment changes, such as increased microviscosity and depolarisation. These changes are strongly related to cell death by inducing mitochondrial swelling with excessive fission and fusion. We suggest a potential mechanism from mitochondrial oxidative stress to cell death based on proteomic analyses and phenomenological observations.

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Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: coordination and photo-induced oxidation

Abstract: Effective chemical strategies, i.e., coordination and coordination-/photo-mediated oxidation, are rationally developed towards modification of amyloidogenic peptides and subsequent control of their aggregation and toxicity.

Cited by 27 publications

References 73 publications

Recent advances of transition Ir(III) complexes as photosensitizers for improved photodynamic therapy

Recent advances of transition Ir(III) complexes as photosensitizers for improved photodynamic therapy

Multifunction‐Harnessed Afterglow Nanosensor for Molecular Imaging of Acute Kidney Injury In Vivo

Analysing the mechanism of mitochondrial oxidation-induced cell death using a multifunctional iridium(III) photosensitiser

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