Ruthenium-Based Photoactivated Chemotherapy

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(43), P. 23397 - 23415

Published: Oct. 17, 2023

Ruthenium(II) polypyridyl complexes form a vast family of molecules characterized by their finely tuned photochemical and photophysical properties. Their ability to undergo excited-state deactivation via photosubstitution reactions makes them quite unique in inorganic photochemistry. As consequence, they have been used, general, for building dynamic molecular systems responsive light but, more particularly, the field oncology, as prodrugs new cancer treatment modality called photoactivated chemotherapy (PACT). Indeed, coordination bond be selectively broken under visible irradiation offers fascinating perspectives oncology: it is possible make poorly toxic agents dark that become activated toward cell killing simple compound inside tumor. In this Perspective, we review most important concepts behind PACT idea, relationship between ruthenium compounds used those related phototherapeutic approach photodynamic therapy (PDT), discuss questions about real-life applications clinic. We conclude Perspective with challenges an outlook.

Language: Английский

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Narrow Bandgap Schottky Heterojunction Sonosensitizer with High Electron–Hole Separation Boosted Sonodynamic Therapy in Bladder Cancer

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: March 29, 2024

Abstract Sonodynamic therapy (SDT) is applied to bladder cancer (BC) given its advantages of high depth tissue penetration and nontoxicity due the unique anatomical location near abdominal surface. However, low electron–hole separation efficiency wide bandgap sonosensitizers limit effectiveness SDT. This study aims develop a TiO 2 ‐Ru‐PEG Schottky heterojunction sonosensitizer with narrow for SDT in BC. Density functional theory (DFT) calculations experiments collectively demonstrate that reduced characteristic crystalline‐amorphous interface formed by deposition ruthenium (Ru) within shell layer . Thanks enhancement oxygen adsorption efficient pairs, promotes generation reactive species (ROS) under ultrasound (US) irradiation, resulting cell cycle arrest apoptosis tumor cells. The vivo results prove boosted subcutaneous orthotopic models while exhibiting good safety. adopts complex optimizing sonosensitizers, contributing progress improvement strategies presenting paradigm BC therapy.

Language: Английский

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Recent advances for enhanced photodynamic therapy: from new mechanisms to innovative strategies

Chemical Science, Journal Year: 2024, Volume and Issue: 15(31), P. 12234 - 12257

Published: Jan. 1, 2024

Photodynamic therapy (PDT) has been developed as a potential cancer treatment approach owing to its non-invasiveness, spatiotemporal control and limited side effects. Currently, great efforts have made improve the PDT effect in terms of safety efficiency. In this review, we highlight recent advances innovative strategies for enhanced PDT, including (1) development novel radicals, (2) design activatable photosensitizers based on TME light, (3) photocatalytic NADH oxidation damage mitochondrial electron transport chain. Additionally, new mechanisms are also presented an inspiration PSs. Finally, discuss current challenges future prospects clinical practice these strategies. It is hoped that review will provide angle understanding relationship between intratumoural redox environment mechanisms, ideas smart systems.

Language: Английский

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Control of biomedical nanoparticle distribution and drug release in vivo by complex particle design strategies

European Journal of Pharmaceutics and Biopharmaceutics, Journal Year: 2025, Volume and Issue: unknown, P. 114634 - 114634

Published: Jan. 1, 2025

Language: Английский

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Ruthenium(II) Polypyridyl Complexes Containing COUBPY Ligands as Potent Photosensitizers for the Efficient Phototherapy of Hypoxic Tumors

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7360 - 7376

Published: Feb. 15, 2025

Hypoxia, a hallmark of many solid tumors, is linked to increased cancer aggressiveness, metastasis, and resistance conventional therapies, leading poor patient outcomes. This challenges the efficiency photodynamic therapy (PDT), which relies on generation cytotoxic reactive oxygen species (ROS) through irradiation photosensitizer (PS), process partially dependent levels. In this work, we introduce novel family potent PSs based ruthenium(II) polypyridyl complexes with 2,2′-bipyridyl ligands derived from COUPY coumarins, termed COUBPYs. Ru-COUBPY exhibit outstanding in vitro cytotoxicity against CT-26 cells when irradiated light within phototherapeutic window, achieving nanomolar potency both normoxic hypoxic conditions while remaining nontoxic dark, impressive phototoxic indices (>30,000). Their ability generate Type I II ROS underpins their exceptional PDT efficiency. The lead compound study, SCV49, shows favorable vivo pharmacokinetic profile, excellent toxicological tolerability, tumor growth inhibition mice bearing subcutaneous tumors at doses as low 3 mg/kg upon deep-red (660 nm). These results allow us propose SCV49 strong candidate for further preclinical development, particularly treating large tumors.

Language: Английский

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DNA-Targeting Bioactive Photosensitizer for Chemo-Photodynamic Therapy of Malignant Tumor

ACS Materials Letters, Journal Year: 2024, Volume and Issue: 6(3), P. 969 - 975

Published: Feb. 15, 2024

The design of a biologically active photosensitizer that effectively combines chemotherapy and photodynamic therapy remains significant challenge. This article introduces DNA targeted photosensitizer, CQA, which integrates the alkylating moiety chlormethine with photosensitizing moiety. Through damage experiments molecular docking, CQA has been demonstrated to act as an effective targeting damaging chemotherapeutic agent via chlormethine. Meanwhile, can substantially amplify under light irradiation. Such enhancement is attributed introduction anthraquinone group, possesses good redox properties acts electron acceptor promote transfer. Consequently, efficiently generates both type-I type-II reactive oxygen species (ROS), exerting excellent (PDT) effect. antitumor efficacy validated results from in vivo tumor growth experiments, H&E staining, IHC analyses. this study emphasizes enhanced ROS generation, underscoring crucial role efficient synergistic chemo- advancing cancer treatment strategies.

Language: Английский

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Near–Infrared Heptamethine Cyanine Photosensitizers with Efficient Singlet Oxygen Generation for Anticancer Photodynamic Therapy

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

Published: July 31, 2024

Abstract Near‐infrared photosensitizers are valuable tools to improve treatment depth in photodynamic therapy (PDT). However, their low singlet oxygen ( 1 O 2 ) generation ability, indicated by quantum yield, presents a formidable challenge for PDT. To overcome this challenge, the heptamethine cyanine was decorated with biocompatible S Scy7 and Se Secy7 atom. We observe that exhibits redshift main absorption ~840 nm an ultra‐efficient capacity. The emergence of strong intramolecular charge transfer effect between atom polymethine chain considerably narrows energy gap (0.51 eV), heavy strengthens spin–orbit coupling (1.44 cm −1 ), both which greatly improved high triplet state yield (61 %), determines . Therefore, demonstrated excellent capacity, is ~24.5‐fold indocyanine green, ~8.2‐fold IR780, ~1.3‐fold methylene blue under low‐power‐density 850 irradiation (5 mW −2 ). considerable phototoxicity toward cancer cells buried 12 mm tissue. Nanoparticles formed encapsulating within amphiphilic polymers lecithin, promising antitumor anti‐pulmonary metastatic effects, exhibiting remarkable potential advancing PDT deep tissues.

Language: Английский

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Photoresponsive Drug Delivery Systems: Challenges and Progress

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(38)

Published: June 12, 2024

Abstract Photoresponsive drug delivery systems (PDDSs) have emerged as a promising toolbox for delivery, offering precise control over the site, duration, and dosage of light‐triggered medication. It allows controlled release, photo‐triggered targeting, diagnosis, treatment, improving precision efficacy therapies various diseases. Despite progress in designing different PDDSs, clinical translation has been limited due to obstacles. Herein, this review article focuses on three critical challenges PDDSs: 1) accumulation at diseased lesions, 2) light irradiation, 3) penetration tissues. Also, summarizes discusses current advancements strategies address these challenges. Overall, it emphasizes need clarify from bench bedside develop enhance therapeutic outcomes, increase compatibility patient compliance, unlock possibilities therapies.

Language: Английский

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Dinuclear Tridentate Ru(II) Complex with Strong Near-Infrared Light-Triggered Anticancer Activity

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(13), P. 11125 - 11137

Published: June 21, 2024

The design of the dinuclear Ru(II) complex (Ru2) with strong near-infrared (NIR) absorption properties has been reported for efficient anticancer phototherapy. Under 700 nm LED light excitation, Ru2 exhibited remarkable synergistic type I/II photosensitization ability and photocatalytic activity toward intracellular biomolecules. showed impressive light-triggered under normoxia hypoxia compared clinically used photosensitizer Chlorin e6. mechanistic studies that induced redox imbalance perturbed energy metabolism biosynthesis in A549 cancer cells. Overall, this work provides a new strategy developing metal-based complexes phototherapy NIR light.

Language: Английский

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A NIR‐II‐Emissive Organic Nanomedicine with Biomimetic Engineering for High‐Contrast Targeted Bioimaging and Multiple Phototherapies of Pancreatic Tumors

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Abstract Recent advances are achieved in the design and development of efficient organic photosensitizers (PSs), especially with fluorescence imaging navigation second near‐infrared (NIR‐II, 1000–1700 nm) region. However, there simply a handful NIR‐II emissive PSs oxygen‐independent capability due to scarcity high‐performance NIR‐responsive materials targeted delivery. Herein, NIR‐II‐emissive nanomedicine biomimetic engineering for multiple phototherapies pancreatic tumors is reported. An A‐D‐A‐type conjugated small‐molecule TPC designed used prepare water‐dispersive nanoparticles, which demonstrated high efficiency type I II photodynamic performances, good photothermal conversion 57%, bright emission quantum yield 9.8% under 808 nm light irradiation. With cancer cell membrane camouflage, high‐resolution bioimaging whole‐body blood vessels tumors. Antitumor experiments tumor elimination biosafety This work versatile enhanced tumor‐targeting superior phototheranostics, providing feasible idea evolution theranostics.

Language: Английский

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