Luminescent Ruthenium(II) Polypyridine Complexes for a Wide Variety of Biomolecular and Cellular Applications

Shum, Justin; Leung, Peter Kam‐Keung; Lo, Kenneth Kam‐Wing

doi:10.1021/acs.inorgchem.8b02979

Cited by 138 publications

(124 citation statements)

References 97 publications

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“…To overcome these limitations, there is a need for the development of new classes of PSs. Among others, the use of transition metal complexes [6][7][8][9][10][11] and especially, Ru(II) polypyridine complexes are gaining momentum due to their attractive photophysical and chemical properties (i.e., strong luminescence, high singlet oxygen production, high chemical, and photophysical stability) [12][13][14][15][16][17][18][19][20][21][22] , with the compound TLD-1433 having just entered phase II clinical trials for the treatment of non-muscle invasive bladder cancer [23][24][25] . Despite these remarkable properties, the vast majority of Ru(II) polypyridine complexes are excited using either blue or UV-A light.…”

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confidence: 99%

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

et al. 2020

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The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E′)-4,4′-bisstyryl-2,2′-bipyridine ligands show impressive 1-and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation.

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confidence: 99%

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

et al. 2020

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“…As mentioned in the introduction of this review, there are many requirements an optimized nanovector needs to fulfil, i.e., biocompatibility, a controlled size between 20 and 200 nm, the highest possible loading, no release of the photosensitizer before the delivery site and an efficient ROS formation upon irradiation. To achieve this, the inherent properties of the photosensitizer itself are essential, but this is beyond the scope of this review, and the literature is rich on this point [23,37,[126][127][128][129][130]. Our aim in this part is to focus on the vector and examine the different methodologies that can be used to optimize the final PDT efficiency.…”

Section: Formulation Optimizationmentioning

confidence: 99%

Rational design of block copolymer self-assemblies in photodynamic therapy

Demazeau¹,

Gibot²,

Mingotaud³

et al. 2020

Beilstein J. Nanotechnol.

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Photodynamic therapy is a technique already used in ophthalmology or oncology. It is based on the local production of reactive oxygen species through an energy transfer from an excited photosensitizer to oxygen present in the biological tissue. This review first presents an update, mainly covering the last five years, regarding the block copolymers used as nanovectors for the delivery of the photosensitizer. In particular, we describe the chemical nature and structure of the block copolymers showing a very large range of existing systems, spanning from natural polymers such as proteins or polysaccharides to synthetic ones such as polyesters or polyacrylates. A second part focuses on important parameters for their design and the improvement of their efficiency. Finally, particular attention has been paid to the question of nanocarrier internalization and interaction with membranes (both biomimetic and cellular), and the importance of intracellular targeting has been addressed.

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“…Among the new classes investigated, coordinatively saturated, inert Ru(II) polypyridyl complexes are receiving increasing attention due to their promising anticancer and antimicrobial activity as chemotherapeutic agents as well as photodynamic therapy (PDT) photosensitizers (PSs). [6][7][8][9][10][11][12][13][14][15][16][17] Very importantly, one of Mc Farland and co-workers' ruthenium-based PDT PSs, namely TLD-1433, just completed phase I clinical trial as a PDT PS against bladder cancer. [10] In the field of ruthenium-based PDT PSs, most studies in the literature are based on a [Ru(bipy/phen/bphen/dppz)3] 2+ (bipy = 2,2'-bipyridine, phen =1,10-phenanthroline, bphen = 4,7-diphenyl-1,10-phenanthroline, dppz = dipyrido[3,2-a:2′,3′-c]phenazine) scaffold due to their interesting redox properties, long excited-state lifetimes as well as intense luminescence.…”

Section: Introductionmentioning

confidence: 99%

Systematic investigation of the antiproliferative activity of a series of ruthenium terpyridine complexes

Karges

Blacque

Jakubaszek

et al. 2019

Journal of Inorganic Biochemistry

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Due to acquired resistance or limitations of the currently approved drugs against cancer, there is an urgent need for the development of new classes of compounds. Among others, there is an increasing attention towards the use of Ru(II) polypyridyl complexes. Most studies in the literature were made on complexes based on the coordination of N-donating bidentate ligands to the ruthenium core whereas studies on 2,2´:6´, 2´´-terpyridine (terpy) coordinating ligands are relatively scare. However, several studies have shown that [Ru(terpy)2] 2+ derivatives are able bind to DNA through various binding modes making these compounds potentially suitable as chemotherapeutic agents. Additionally, light irradiation of these compounds was shown to enable DNA cleavage, highlighting their potential use as photosensitizers (PSs) for photodynamic therapy (PDT). In this work, we present the systematic investigation of the potential of 7 complexes of the type [Ru(terpy)(terpy-X)]2+ (X = H (1), Cl (2), Br (3), OMe (4), COOH (5), COOMe (6), NMe2 (7)) as potential chemotherapeutic agents and PDT PSs. Importantly, six of the seven complexes were found to be stable in human plasma as well as photostable in acetonitrile upon continuous light irradiation (480 nm). The determination of the distribution coefficient logP values for the 7 complexes revealed their good water solubility. Complex 7 was found to be cytotoxic in the micromolar range in the dark as well as to have some phototoxicity upon light exposure at 480 nm in non-cancerous retinal pigment epithelium (RPE-1) and cancerous human cervical carcinoma (HeLa) cells.

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Luminescent Ruthenium(II) Polypyridine Complexes for a Wide Variety of Biomolecular and Cellular Applications

Cited by 138 publications

References 97 publications

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

Rational design of block copolymer self-assemblies in photodynamic therapy

Systematic investigation of the antiproliferative activity of a series of ruthenium terpyridine complexes

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