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

Diego Abad-Montero,

Albert Gandioso, E. Izquierdo

и другие.

Journal of the American Chemical Society, Год журнала: 2025, Номер 147(9), С. 7360 - 7376

Опубликована: Фев. 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.

Язык: Английский

Engineered Metallacycle‐Based Supramolecular Photosensitizers for Effective Photodynamic Therapy DOI

Le Tuan Tu,

Chonglu Li,

Xiaoxing Xiong

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(15)

Опубликована: Фев. 14, 2023

Abstract Although metallacycle‐based supramolecular photosensitizers (PSs) have attracted increasing attention in biomedicine, their clinical translation is still hindered by inherent dark toxicity. Herein, we report what to our knowledge the first example of a molecular engineering approach building blocks metallacycles for constructing series PSs ( RuA–RuD ), with aim simultaneously reducing toxicity and enhancing phototoxicity, consequently obtaining high phototoxicity indexes (PI). Detailed vitro investigations demonstrate that display cancer cellular uptake remarkable antitumor activity even under hypoxic conditions. Notably, RuD exhibited no displayed highest PI value (≈406). Theoretical calculations verified has largest steric hindrance lowest singlet‐triplet energy gap (Δ E ST , 0.61 eV). Further vivo studies confirmed allows safe effective phototherapy against A549 tumors.

Язык: Английский

Процитировано

77
Structurally Simple Osmium(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy in the Near Infrared** DOI Creative Commons

A. Mani,

Tao Feng, Albert Gandioso

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(20)

Опубликована: Март 14, 2023

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7-diphenyl-1,10-phenanthroline)2 L]2+ were synthesized as photosensitizers for photodynamic therapy by varying nature ligand L. Thanks to pronounced π-extended structure ligands and heavy atom effect provided osmium center, these exhibit a high absorption in near-infrared (NIR) region (up 740 nm), unlike related ruthenium complexes. This led promising phototoxicity vitro against cancer cells cultured 2D cell layers but also multicellular tumor spheroids upon irradiation at nm. The complex (2,2'-bipyridine)]2+ was found be most efficient various lines, with indexes. Experiments on CT26 tumor-bearing BALB/c mice indicate that OsII could significantly reduce growth following nm laser irradiation. biological window this structurally simple makes it photosensitizer treatment.

Язык: Английский

Процитировано

45
Smart One‐for‐All Agent with Adaptive Functions for Improving Photoacoustic /Fluorescence Imaging‐Guided Photodynamic Immunotherapy DOI
Heqi Gao,

Xinwen Qi,

Jingtian Zhang

и другие.

Small Methods, Год журнала: 2023, Номер 7(5)

Опубликована: Фев. 19, 2023

Multifunctional phototheranostics that integrate several diagnostic and therapeutic strategies into one platform hold great promise for precision medicine. However, it is really difficult molecule to possess multimodality optical imaging therapy properties all functions are in the optimized mode because absorbed photoenergy fixed. Herein, a smart one-for-all nanoagent photophysical energy transformation processes can be facilely tuned by external light stimuli developed precise multifunctional image-guided therapy. A dithienylethene-based designed synthesized has two light-switchable forms. In ring-closed form, most of dissipates via nonradiative thermal deactivation photoacoustic (PA) imaging. ring-open possesses obvious aggregation-induced emission features with excellent fluorescence photodynamic properties. vivo experiments demonstrate preoperative PA help delineate tumors high-contrast manner, intraoperative able sensitively detect tiny residual tumors. Furthermore, induce immunogenic cell death elicit antitumor immunity significantly suppress solid This work develops agent related phototheranostic light-driven structure switch, which promising biomedical applications.

Язык: Английский

Процитировано

27
Theoretical Investigation of Ru(II) Complexes with Long Lifetime and a Large Two-Photon Absorption Cross-Section in Photodynamic Therapy DOI

Xue Wei,

Wei-Bo Cui,

Gui-Ya Qin

и другие.

Journal of Medicinal Chemistry, Год журнала: 2023, Номер 66(6), С. 4167 - 4178

Опубликована: Март 8, 2023

Two-photon photodynamic therapy (TP-PDT), as a new method for cancer, has shown unique advantages in tumors. A low two-photon absorption cross-section (δ) the biologic spectral window and short triplet state lifetime are important issues faced by current photosensitizers (PSs) TP-PDT. In this paper, photophysical properties of series Ru(II) complexes were studied density functional theory time-dependent methods. The electronic structure, one- properties, type I/II mechanisms, lifetime, solvation free energy calculated. results showed that substitution methoxyls pyrene groups greatly improved complex. Furthermore, addition acetylenyl subtly enhanced δ. Overall, complex 3b possess large δ(1376 GM), long (136 μs), better energy. It is hoped it can provide valuable theoretical guidance design synthesis efficient PSs experiment.

Язык: Английский

Процитировано

27
Nanocomposite of chitosan/gelatin/carbon quantum dots as a biocompatible and efficient nanocarrier for improving the Curcumin delivery restrictions to treat brain cancer DOI
Shima Ostovar, Mehrab Pourmadadi, Amin Shamsabadipour

и другие.

International Journal of Biological Macromolecules, Год журнала: 2023, Номер 242, С. 124986 - 124986

Опубликована: Май 24, 2023

Язык: Английский

Процитировано

24
Organoruthenium-bipyridyl complexes – A platform for diverse chemistry and applications DOI
Chayan Pandya, Akella Sivaramakrishna

Coordination Chemistry Reviews, Год журнала: 2024, Номер 504, С. 215655 - 215655

Опубликована: Янв. 25, 2024

Язык: Английский

Процитировано

12
Synthesis, Crystallographic Structure, Theoretical Analysis, Molecular Docking Studies, and Biological Activity Evaluation of Binuclear Ru(II)-1-Naphthylhydrazine Complex DOI Open Access
Thomas Eichhorn,

Franz Kolbe,

Stefan Mišić

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 24(1), С. 689 - 689

Опубликована: Дек. 30, 2022

Ruthenium(II)–arene complexes have gained significant research interest due to their possible application in cancer therapy. In this contribution two new are described, namely [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-1-N,N′-naphthyl)]X (X = Cl, 1; PF6, 2), which were fully characterized by IR, NMR, and elemental microanalysis. Furthermore, the structure of 2 solid state was determined a single crystal X-ray crystallographic study, confirming composition crystals as 2·2MeOH. The Hirshfeld surface analysis employed for investigation interactions that govern structural data out 2·2MeOH used theoretical cationic part [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-1-N,N′-naphthyl)]+ (2a) is common both 1 2. density functional theory, at B3LYP/6-31+G(d,p) basis set H, C, N, Cl atoms LanL2DZ Ru ions, optimization 2a structure. natural bond orbital quantum theory molecules analyses quantify intramolecular interactions. reproduction experimental IR NMR spectra proved applicability chosen level theory. binding bovine serum albumin examined spectrofluorimetry molecular docking, with complementary results obtained. Compound acted radical scavenger towards DPPH• HO• radicals, along high activity prostate colon cell lines.

Язык: Английский

Процитировано

35
Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions DOI Creative Commons
Gina Elena Giacomazzo, Luca Conti, Camilla Fagorzi

и другие.

Inorganic Chemistry, Год журнала: 2023, Номер 62(20), С. 7716 - 7727

Опубликована: Май 10, 2023

Ruthenium(II) polypyridyl complexes (RPCs) are gaining momentum in photoactivated chemotherapy (PACT), thanks to the possibility of overcoming classical reliance on molecular oxygen photodynamic therapy while preserving selective drug activation by using light. However, notwithstanding intriguing perspectives, translation such an approach development new antimicrobials has been only barely considered. Herein, MTZH-1 and MTZH-2, two novel analogues metronidazole (MTZ), a mainstay treatment anaerobic bacterial infections, were designed inserted strained ruthenium [Ru(tpy)(dmp)(MTZ-1)]PF6 (Ru2) [Ru(tpy)(dmp)(MTZ-2)]PF6 (Ru3) (tpy = terpyridine, dmp 2,9-dimethyl-1,10-phenanthroline) (Chart 1). Analogously parental compound [Ru(tpy)(dmp)(5NIM)]PF6 (Ru1) (5-nitroimidazolate), Ru(II)-imidazolate coordination MTZ derivatives resulted promising Ru(II) photocages, capable easily unleash bioactive ligands upon light irradiation increase antibacterial activity against Bacillus subtilis, which was chosen as model Gram-positive bacteria. The photoreleased 5-nitroimidazole-based led remarkable phototoxicities under hypoxic conditions (<1% O2), with lead Ru3 that exhibited highest potency across series, being comparable one clinical MTZ. Besides, chemical architectures made their interaction NimAunfavorable, NimA reductases responsible for resistance antibiotics, thus hinting at possible use combat antimicrobial resistance. This work may therefore provide fundamental knowledge design photoresponsive tools be used fight infectious diseases. For first time, effectiveness "photorelease therapy" therapeutically relevant demonstrated.

Язык: Английский

Процитировано

21
Perturbing tumor cell metabolism with a Ru(II) photo-redox catalyst to reverse the multidrug resistance of lung cancer DOI
Siqi Wei, Hui Liang,

Anyi Dao

и другие.

Science China Chemistry, Год журнала: 2023, Номер 66(5), С. 1482 - 1488

Опубликована: Март 13, 2023

Язык: Английский

Процитировано

16
Polyphosphoester-stabilized cubosomes encapsulating a Ru(II) complex for the photodynamic treatment of lung adenocarcinoma DOI Creative Commons
Luca Casula, Gina Elena Giacomazzo, Luca Conti

и другие.

Journal of Colloid and Interface Science, Год журнала: 2024, Номер 670, С. 234 - 245

Опубликована: Май 16, 2024

The clinical translation of photosensitizers based on ruthenium(II) polypyridyl complexes (RPCs) in photodynamic therapy cancer faces several challenges. To address these limitations, we conducted an investigation to assess the potential a cubosome formulation stabilized water against coalescence utilizing polyphosphoester analog Pluronic F127 as stabilizer and loaded with newly synthesized RPC-based photosensitizer [Ru(dppn)

Язык: Английский

Процитировано

7