Ruthenium polypyridyl squalene derivative: A novel self-assembling lipophilic probe for cellular imaging

Dosio, Franco; Stella, Barbara; Ferrero, Annalisa; Garino, Claudio; Zonari, Daniele; Arpicco, Silvia Maria; Cattel, Luigi; Giordano, Sara; Gobetto, Roberto

doi:10.1016/j.ijpharm.2012.07.022

Cited by 18 publications

(15 citation statements)

References 38 publications

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“…7d,7e,24 They affect cell viability similarly to Ru(III) polypyridine complexes, which also have ED 50 (72 h) values ≥300 μM in MCF-7 and HT-29 cell lines. 25 It is interesting to note that the europium compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid containing no antenna moiety, [Eu-DOTA] − , has a negligible effect on cell viability from 0 to 500 μM with a 72 h incubation. 26 Thus, with respect to cell viability, [Tb -1 ] and [Tb -2 ] − are preferred for cellular imaging applications compared to [Tb -3 ].…”

Section: Resultsmentioning

confidence: 99%

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Effect of Lanthanide Complex Structure on Cell Viability and Association

et al. 2014

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A systematic study of the effect of hydrophobicity and charge on the cell viability and cell association of lanthanide metal complexes is presented. The terbium luminescent probes feature a macrocyclic polyaminocarboxylate ligand (DOTA) in which the hydrophobicity of the antenna and that of the carboxyamide pendant arms are independently varied. Three sensitizing antennas were investigated in terms of their function in vitro: 2-methoxyisophthalamide (IAM(OMe)), 2-hydroxyisophthalamide (IAM), and 6-methylphenanthridine (Phen). Of these complexes, Tb-DOTA-IAM exhibited the highest quantum yield, although the higher cell viability and more facile synthesis of the structurally related Tb-DOTA-IAM(OMe) platform renders it more attractive. Further modification of this latter core structure with carboxyamide arms featuring hydrophobic benzyl, hexyl, and trifluoro groups as well as hydrophilic amino acid based moieties generated a family of complexes that exhibit high cell viability (ED50 > 300 μM) regardless of the lipophilicity or the overall complex charge. Only the hexyl-substituted complex reduced cell viability to 60% in the presence of 100 μM complex. Additionally, cellular association was investigated by ICP-MS and fluorescence microscopy. Surprisingly, the hydrophobic moieties did not increase cell association in comparison to the hydrophilic amino acid derivatives. It is thus postulated that the hydrophilic nature of the 2-methoxyisophthalamide antenna (IAM(OMe)) disfavors the cellular association of these complexes. As such, responsive luminescent probes based on this scaffold would be appropriate for the detection of extracellular species.

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Section: Resultsmentioning

confidence: 99%

“…7d Unfortunately, further comparisons with cellular accumulation values reported in the literature are limited due to differences in the method of data collection (ICP-MS vs flow cytometry 7a,21a,29 ), and data presentation of metal per amount of protein or per cell. 7e,24,25,28,30 …”

Section: Resultsmentioning

confidence: 99%

Effect of Lanthanide Complex Structure on Cell Viability and Association

et al. 2014

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“…Gobetto and co‐workers described the conjugation of the luminescent Ru(II) polypyridyl complex, [Ru(bpy) 2 BPPBI‐hx](PF6) 2 ( Ru20 , BPPBI = 6‐[2‐(4‐methyl‐pyridin‐2‐yl)‐1H‐benzoimidazol‐1‐yl]‐hexylamine) to SQ‐NHS via an amide bond (Figure 5e). [ 53 ] The resulting conjugate, Ru20‐SQ , could self‐assemble into narrowly dispersed 300 nm nanoparticles using a nanoprecipitation technique. Ru20‐SQ was found to be nontoxic toward HT‐29 colorectal (IC 50 = 380 × 10 −6 m ) and MCF‐7 breast cancer cell lines (IC 50 = 110 × 10 −6 m ).…”

Section: Organic Nanoparticlesmentioning

confidence: 99%

Incorporation of Ru(II) Polypyridyl Complexes into Nanomaterials for Cancer Therapy and Diagnosis

2020

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Ru(II) metal center. [2] They absorb light and emit wavelength within the red and the near infrared (NIR) spectral regions and possess large Stokes shift, long luminescence lifetime, and potential twophoton (2P) absorption properties. These characteristics have made them highly desirable across numerous research fields such as catalysis, [3] solar energy, [4] sensors [5] and now across the biomedical field either in diagnostics as cellular imaging tools, luminescent probes of DNA structures or in therapy as new classes of anticancer drugs for chemotherapy and photosensitizers (PSs) for photodynamic therapy (PDT) or photoactivated chemotherapy (PACT). [6-11] Worthy of note, a Ru(II) polypyridyl compound (TLD1433) has recently entered phase II clinical trials in Canada for the treatment of nonmuscle invasive bladder cancer as a PS for PDT. [12] However, these complexes still suffer from some drawbacks such as poor water solubility, lack of targeting capability, nonspecific distribution, systemic toxicity and hence, low therapeutic index hampering their translation into the clinic. One strategy to address those medical challenges is to use nanomedicine. Nanomedicine is the application of sub-micron particles (i.e., nanoparticles) in the field of medicine. The materials used for the synthesis and/ or formulation of nanoparticles are extremely diverse, ranging from organic to inorganic molecules (Figure 1). [13] The unique features of nanoparticles including small size, high surface area, surface chemistry, water solubility and multifunctionality make them highly interesting for drug delivery purposes. [14,15] Owing to their size, nanoparticles can passively accumulate to solid tumors while sparing healthy cells thanks to the enhanced permeation and retention (EPR) effect. [16] The EPR effect exploits the abnormalities of tumor vasculature, namely hypervascularity, atypical vascular architecture, leaky vasculature, and lack of lymphatic drainage. This results in the efficient extravasation of nanoparticles from the tumor vasculature and their retention in the tumor interstitium. Therefore, drug incorporation into nanoparticles provides significant improvements in pharmacokinetics, solubility, toxicity, and biodistribution when compared to freely administered molecules, reducing adverse side effects observed with conventional medicine. However, to take full advantage of the EPR effect, nanoparticles must remain in circulation long enough for tumor accumulation. PEGylation, which refers to modification with poly(ethylene glycol) (PEG) chains or PEG copolymers (e.g., Jeffamine), is the most common strategy for imparting stealth properties to nanoparticles. [17] The presence of PEG enables steric stabilization Ru(II) polypyridyl complexes are compounds of great interest in cancer therapy due to their unique photophysical, photochemical, and biological properties. For effective treatment, they must be able to penetrate tumor cells effectively and selectively. The development of nanoscale carriers capable of delivering Ru(I...

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“…Luminescent ruthenium(II) complexes are of interest of due to their applications in photochemical molecular devices (PMD) such as OLED devices, dye-sensitized solar cells (DSSC), photosensitizers in artificial photosynthesis, sensors, DNA dynamic probes, lipid probes and fluorescence polarization immunoassays (FPI) [1][2][3][4][5][6][7][8][9][10][11]. Recent descriptions of the photochemistry of coordination compounds of ruthenium(II) indicate that they can fulfill many of the functions necessary for these devices [1].…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic characterization of chloride and pseudohalide ruthenium(II) complexes with 4-(4-nitrobenzyl)pyridine

Maroń

Małecki

2014

Transition Met Chem

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Chloride, isocyanate and isothiocyanate hydride carbonyl ruthenium(II) complexes of 4-(4-nitrobenzyl)pyridine were synthesized from the precursor complex [RuHCl(CO)(PPh 3 ) 3 ] and characterized by IR, NMR, UV-Vis spectroscopy and X-ray crystallography. The electronic structures of the complexes were investigated by means of DFT calculations, based on their crystal structures. The spinallowed singlet-singlet electronic transitions of the complexes were calculated by time-dependent DFT, and the UVVis spectra are discussed on this basis. The emission properties of the complexes were studied at ambient temperature, and the quantum yields of fluorescence, the lifetimes and nature of the excited states are discussed. The chloride and isothiocyanate complexes are practically nonemissive, with quantum yields under 0.01 %. Interpretation of spectra, supported by TD-DFT calculations, indicates that in this energy region, the transitions have MLCT character with admixture of LLCT (chloride and isothiocyanate complexes). The dominant LLCT character was visible in the case of the most emissive (isocyanate) complex. The low values of the lifetimes and quantum yields for these complexes indicate the influence of the metal center in the emission process.

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Ruthenium polypyridyl squalene derivative: A novel self-assembling lipophilic probe for cellular imaging

Cited by 18 publications

References 38 publications

Effect of Lanthanide Complex Structure on Cell Viability and Association

Effect of Lanthanide Complex Structure on Cell Viability and Association

Incorporation of Ru(II) Polypyridyl Complexes into Nanomaterials for Cancer Therapy and Diagnosis

Spectroscopic characterization of chloride and pseudohalide ruthenium(II) complexes with 4-(4-nitrobenzyl)pyridine

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