Metallopolymer strategy to explore hypoxic active narrow-bandgap photosensitizers for effective cancer photodynamic therapy

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 2, 2024

Abstract Practical photodynamic therapy calls for high-performance, less O 2 -dependent, long-wavelength-light-activated photosensitizers to suit the hypoxic tumor microenvironment. Iridium-based exhibit excellent photocatalytic performance, but in vivo applications are hindered by conventional -dependent Type-II photochemistry and poor absorption. Here we show a general metallopolymerization strategy engineering iridium complexes exhibiting Type-I enhancing absorption intensity blue near-infrared region. Reactive oxygen species generation of metallopolymer Ir-P1 , where atom is covalently coupled polymer backbone, over 80 times higher than that its mother without under 680 nm irradiation. This also works effectively when directly included ( Ir-P2 ) backbones, wide generality. The nanoparticles efficient •− conjugated with integrin αvβ3 binding cRGD achieve targeted therapy.

Language: Английский

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Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular Solutions

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(41)

Published: June 20, 2023

The importance of transition metal catalysis is exemplified by its wide range applications, for example in the synthesis chemicals, natural products, and pharmaceuticals. However, one relatively new application carrying out new-to-nature reactions inside living cells. complex environment a cell not welcoming to catalysts, as diverse biological components have potential inhibit or deactivate catalyst. Here we review current progress field catalysis, evaluation efficiency cells under (relevant) conditions. Catalyst poisoning ubiquitous problem this field, propose that future research into development physical kinetic protection strategies may provide route improve reactivity catalysts

Language: Английский

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Recent Advances in Bioconjugated Transition Metal Complexes for Cancer Therapy

Applied Sciences, Journal Year: 2023, Volume and Issue: 13(9), P. 5561 - 5561

Published: April 29, 2023

The introduction of biologically relevant organic moieties in the coordination sphere transition metal complexes has recently become a well-established strategy to increase selectivity and biocompatibility metallodrugs. In this review, major advances achieved area research last three years are described detail. Particular attention is given bearing main biomolecules life: carbohydrates, lipids, nucleotides, proteins vitamins. Each paragraph summarizes synthetic employed obtain interest as well most interesting biological results obtained with these potential Moreover, structure–activity relationships observed by different groups discussed, goal suggesting reader ligand/metal centre combinations that provide promising fight against cancer. Some compounds examined review other bioconjugated published recent decades exhibit towards cancer cells over normal ones specific mode action. These latter aspects basis what commonly known anticancer target therapy.

Language: Английский

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Intracellular Synthesis of Indoles Enabled by Visible-Light Photocatalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 2895 - 2900

Published: Jan. 26, 2024

Performing abiotic synthetic transformations in live cell environments represents a new, promising approach to interrogate and manipulate biology uncover new types of biomedical tools. We now found that photocatalytic bond-forming reactions can be added the toolbox bioorthogonal chemistry. Specifically, we demonstrate exogenous styryl aryl azides converted into indoles inside living mammalian cells under conditions.

Language: Английский

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Bithiophene‐Functionalized Infrared Two‐Photon Absorption Metal Complexes as Single‐Molecule Platforms for Synergistic Photodynamic, Photothermal, and Chemotherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(27)

Published: April 24, 2024

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, chemotherapy. The significant two-photon absorption at 808 nm remarkable singlet oxygen superoxide anion production in aqueous solution cells when exposed to infrared irradiation. most potent Ru(II) complex Ru7 enters tumor via the rare macropinocytosis, locates both nuclei mitochondria, regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase RNA polymerase inhibition their effects photoactivated apoptosis, ferroptosis cleavage. exhibits high efficacy vivo malignant melanoma cisplatin-resistant non-small cell lung cancer tumors, a 100 % survival rate of mice, low toxicity normal residual rate. Such an activatable metal may contribute new generation single-molecule-based integrated diagnosis treatment address drug resistance clinical practice phototherapy large, deeply located solid tumors.

Language: Английский

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Bioorthogonal catalysis in complex media: Consequences of using polymeric scaffold materials on catalyst stability and activity

Catalysis Today, Journal Year: 2023, Volume and Issue: 418, P. 114116 - 114116

Published: March 14, 2023

Bioorthogonal catalysis using transition-metal-based complexes (TMCs) is a promising approach for converting substrates to desired products in complex cellular media. Notably, the situ activation of prodrugs or synthesis active drugs with aim complement existing treatments diseases such as cancer has received significant attention. Whereas focus initially been on optimizing ligands enhance activity and stability metal complexes, more recently benign effects compartmentalization catalyst into homogeneous heterogeneous scaffolds have unveiled. Such tailor-made carrier materials not only afford catalysts but also permit guide site interest vivo applications. This review will emphasize potential synthetic amphiphilic polymers that form compartmentalized nanostructures TMCs. The use well established field nanomedicine i.e. drug delivery purposes, their application TMCs less explored. Since are readily functionalized targeting moieties, they can act versatile carriers. After short overview state-of-the-art bioorthogonal ligand-based TMCs, we summarize advances natural catalysis. We end this by highlighting recent media embedded formed polymers. combination polymer science may open up new opportunities advancing exciting therapeutic

Language: Английский

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Bioorthogonal Synthetic Chemistry Enabled by Visible‐Light Photocatalysis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(47)

Published: Aug. 13, 2024

Abstract The field of bioorthogonal chemistry has revolutionized our ability to interrogate and manipulate biological systems at the molecular level. However, range chemical reactions that can operate efficiently in environments without interfering with native cellular machinery, remains limited. In this context, rapidly growing area photocatalysis offers a promising avenue for developing new type tools. inherent mildness, tunability, chemoselectivity, external controllability photocatalytic transformations make them particularly well‐suited applications living systems. This minireview summarizes recent advances technologies, particular focus on their potential enable selective generation designed products within biologically relevant or settings.

Language: Английский

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Smart Bioorthogonal Nanozymes: From Rational Design to Appropriate Bioapplications

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(41)

Published: Aug. 16, 2024

Abstract Bioorthogonal chemistry has provided an elaborate arsenal to manipulate native biological processes in living systems. As the great advancement of nanotechnology recent years, bioorthogonal nanozymes are innovated tackle challenges that emerged practical biomedical applications. uniquely positioned owing their advantages high customizability and tunability, as well good adaptability systems, which bring exciting opportunities for More intriguingly, offers opportunity innovating catalytic materials. In this comprehensive review, significant progresses discussed with both spatiotemporal controllability performance highlight design principles rapid The remaining future perspectives then outlined along thriving field. It is expected review will inspire promote novel nanozymes, facilitate clinical translation.

Language: Английский

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Targeting Pathogenic Formate-Dependent Bacteria with a Bioinspired Metallo–Nitroreductase Complex

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6453 - 6461

Published: March 7, 2023

Nitroreductases (NTRs) constitute an important class of oxidoreductase enzymes that have evolved to metabolize nitro-containing compounds. Their unique characteristics spurred array potential uses in medicinal chemistry, chemical biology, and bioengineering toward harnessing nitro caging groups constructing NTR variants for niche applications. Inspired by how they carry out enzymatic reduction via a cascade hydride transfer reactions, we sought develop synthetic small-molecule system based on hydrogenation mediated transition metal complexes native cofactors. We report the first water-stable Ru–arene complex capable selectively fully reducing nitroaromatics into anilines biocompatible buffered aqueous environment using formate as source. further demonstrated its application activate nitro-caged sulfanilamide prodrug formate-abundant bacteria, specifically pathogenic methicillin-resistant Staphylococcus aureus. This proof concept paves way new targeted antibacterial chemotherapeutic approach leveraging redox–active activation bioinspired nitroreduction.

Language: Английский

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Bleeding the Excited State Energy to the Utmost: Single‐Molecule Iridium Complexes for In Vivo Dual Photodynamic and Photothermal Therapy by an Infrared Low‐Power Laser

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(28)

Published: June 3, 2023

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground excited state properties, well the structural effect on their photophysical biological investigated by spectroscopic, electrochemical, quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells trigger apoptosis related to mitochondrial dysfunction upon irradiation. The complexes, particularly Ir6, demonstrate high indexes a manifest effect. minimal hepato-/nephrotoxicity vitro, significantly inhibits growth tumors vivo under 808 nm laser irradiation photodynamic therapy can be efficiently eliminated from body. These results may contribute development highly phototherapeutic drugs large, deeply buried solid tumors.

Language: Английский

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