scholarly journals Studying the Cellular Distribution of Highly Phototoxic Platinated Metalloporphyrins Using Isotope Labelling

2020 ◽  
Author(s):  
Riccardo Rubbiani ◽  
Wenyu Wu ◽  
Anu Naik ◽  
Michele Larocca ◽  
Lukas Schneider ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Distribution ◽  
Isotopic Labelling ◽  
Isotope Labelling ◽  
Anticancer Properties ◽  
Naturally Occurring ◽  
Icp Ms ◽  
Cell Penetrating

We report the synthesis of novel tetraplatinated metalloporphyrin-based photosensitizers (PSs) for photodynamic therapy (PDT), their characterization, cellular uptake and localization, as well as the determination of their <i>in vitro</i> light-induced anticancer properties. The PSs show excellent phototoxic indexes up to 5800 against HeLa cells, which is, to the best of our knowledge, the highest value reported for any porphyrin so far. Furthermore, isotopic labelling of the porphyrin with a highly enriched <sup>67</sup>Zn isotope was performed in order to determine the distribution ratio of zinc to platinum by ICP-MS, allowing to differentiate between naturally occurring zinc and <sup>67</sup>Zn that was introduced into the cells by the PS. We conclude that the platinum units within the platinum-PS conjugates help to solubilize the PS and, at the same time, act as cell-penetrating vectors, enhancing the efficiency of the PS without causing a significant dark toxicity.<br>

scholarly journals Studying the Cellular Distribution of Highly Phototoxic Platinated Metalloporphyrins Using Isotope Labelling

2020 ◽  
Author(s):  
Riccardo Rubbiani ◽  
Wenyu Wu ◽  
Anu Naik ◽  
Michele Larocca ◽  
Lukas Schneider ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Distribution ◽  
Isotopic Labelling ◽  
Isotope Labelling ◽  
Anticancer Properties ◽  
Naturally Occurring ◽  
Icp Ms ◽  
Cell Penetrating

We report the synthesis of novel tetraplatinated metalloporphyrin-based photosensitizers (PSs) for photodynamic therapy (PDT), their characterization, cellular uptake and localization, as well as the determination of their <i>in vitro</i> light-induced anticancer properties. The PSs show excellent phototoxic indexes up to 5800 against HeLa cells, which is, to the best of our knowledge, the highest value reported for any porphyrin so far. Furthermore, isotopic labelling of the porphyrin with a highly enriched <sup>67</sup>Zn isotope was performed in order to determine the distribution ratio of zinc to platinum by ICP-MS, allowing to differentiate between naturally occurring zinc and <sup>67</sup>Zn that was introduced into the cells by the PS. We conclude that the platinum units within the platinum-PS conjugates help to solubilize the PS and, at the same time, act as cell-penetrating vectors, enhancing the efficiency of the PS without causing a significant dark toxicity.<br>

Determination of S-containing drug metabolites from in vitro and in vivo metabolism studies by using LC-ICP/MS

2012 ◽  
Vol 404 (2) ◽  
pp. 539-551 ◽  
Author(s):  
Cristina Losada ◽  
Joan J. Albertí ◽  
Javier Saurina ◽  
Sonia Sentellas
Keyword(s):  
In Vivo Metabolism ◽  
Drug Metabolites ◽  
Icp Ms

A rapid in vitro assay of cobalamin in human urine and medical tablets using ICP-MS

2009 ◽  
Vol 63 (3) ◽  
Author(s):  
Gai Zhang ◽  
Jianbo Liu ◽  
Zuchao Meng ◽  
Xin Wang
Keyword(s):  
Human Urine ◽  
Inductively Coupled Plasma ◽  
Limit Of Detection ◽  
Rapid Determination ◽  
Vitro Assay ◽  
Cobalt Ions ◽  
Icp Ms ◽  
Relative Standard

AbstractA rapid and simple as well as sensitive inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of cobalamin is described. Cobalamin in human urine and medicine tablet solutions was converted on-line into free cobalt ions in acid medium, the cobalt ions were then detected by ICP-MS. Cobalamin was determined by measuring the increase of integral counts per second intensity, which was linear over the cobalamin concentration range of 1.0 × 10−10 g mL−1 to 8.0 × 10−5 g mL−1, and the limit of detection was 0.05 ng mL−1 (3σ). At the pump rate of 30 rotations per minute, one analysis cycle of cobalamin, including sampling and washing, could be accomplished in 0.5 min with the relative standard deviations of less than 5 %. The proposed procedure was applied successfully in monitoring cobalamin in human urine without any pretreatment process and in rapid determination of cobalamin in multivitamin tablets.

scholarly journals Natural isotope correction improves analysis of protein modification dynamics

2021 ◽  
Author(s):  
Jörn Dietze ◽  
Alienke van Pijkeren ◽  
Anna-Sophia Egger ◽  
Mathias Ziegler ◽  
Marcel Kwiatkowski ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Modification ◽  
High Resolution Mass Spectrometry ◽  
Accurate Determination ◽  
Mass Spectrometry Data ◽  
Stable Isotope Labelling ◽  
Isotope Labelling ◽  
Naturally Occurring ◽  
Correct Estimation

AbstractStable isotope labelling in combination with high-resolution mass spectrometry approaches are increasingly used to analyze both metabolite and protein modification dynamics. To enable correct estimation of the resulting dynamics, it is critical to correct the measured values for naturally occurring stable isotopes, a process commonly called isotopologue correction or deconvolution. While the importance of isotopologue correction is well recognized in metabolomics, it has received far less attention in proteomics approaches. Although several tools exist that enable isotopologue correction of mass spectrometry data, the majority is tailored for the analysis of low molecular weight metabolites. We here present PICor which has been developed for isotopologue correction of complex isotope labelling experiments in proteomics or metabolomics and demonstrate the importance of appropriate correction for accurate determination of protein modifications dynamics, using histone acetylation as an example.

A Radiopharmacological Study without Human Radiation Exposure

1984 ◽  
Vol 22 (01) ◽  
pp. 47-49
Author(s):  
E. H. Graul ◽  
R. Kunkel ◽  
D. Loew
Keyword(s):  
Pharmacological Study ◽  
New Drugs ◽  
New Combination ◽  
In Vitro Diagnostics ◽  
Naturally Occurring ◽  
Nuclear Techniques ◽  
Great Responsibility ◽  
And Control

SummaryThe development, study and control of new drugs today is hardly conceivable without nuclear medicine studies. Nuclear physicians on ethical commissions bear great responsibility in the planning and execution of such studies. In order to protect subjects and patients those nuclear techniques are therefore to be welcome which do not include exposure to radiation. Nuclear techniques used in in-vitro diagnostics (RIA) and the determination of naturally occurring nuclides incorporated in the human body belong to this category. With the aid of a clinico-pharmacological study of a new combination of diuretics it is shown that both methods supply valuable pharmacodynamic evidence.

Photosensitizer-Loaded Magnetic Nanoemulsion for Use in Synergic Photodynamic and Magnetohyperthermia Therapies of Neoplastic Cells

2008 ◽  
Vol 8 (11) ◽  
pp. 5873-5877 ◽  
Author(s):  
Fernando L. Primo ◽  
Marcilene M. A. Rodrigues ◽  
Andreza Ribeiro Simioni ◽  
Zulmira G. M. Lacava ◽  
Paulo C. Morais ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Photodynamic Therapy ◽  
Magnetic Fields ◽  
Zeta Potential ◽  
Cobalt Ferrite ◽  
Hydrodynamic Diameter ◽  
Synergic Effect ◽  
Average Hydrodynamic Diameter

In this study a magnetic nanoemulsion (MNE) was developed from a mixture of two components, namely biodegradable surfactants and biocompatible citrate-coated cobalt ferrite-based magnetic fluid, for entrapment of Zn(II)-Phthalocyanine (ZnPc), the latter a classical photosensitizer (PS) species used in photodynamic therapy (PDT) procedures. The sample's stability was evaluated as a function of time using photocorrelation spectroscopy (PCS) for determination of the average hydrodynamic diameter, diameter dispersion and zeta potential. The ZnPc-loaded magneto nanoemulstion (ZnPc/MNE) formulation was evaluated in vitro assays to access the phototoxicity and the effect of application of AC magnetic fields (magnetohyperthermia damage) after incubation with J774-A1 macrophages cells. Darkness toxicity, phototoxicity and AC magnetic field exposures revealed an enhancement response for combined photodynamic and magnetohyperthermia (MHT) processes, indicating the presence of the synergic effect.

Chlorine e6 in phospholipid nanoparticles with specific targeting and penetrating peptides as prospective composition for photodynamic therapy of malignant neoplasms

2019 ◽  
Vol 65 (6) ◽  
pp. 507-512
Author(s):  
L.V. Kostryukova ◽  
A.D. Plyutinskaya ◽  
A.A. Pankratov ◽  
E.I. Korotkevich ◽  
V.N. Prozorovskiy ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cell Penetrating Peptides ◽  
Malignant Neoplasms ◽  
Specific Targeting ◽  
Phospholipid Nanoparticles ◽  
Cell Penetrating ◽  
Ic50 Values ◽  
Chlorine E6

Cytotoxic and photoinduced activity of chlorine e6 (Ce6) in phospholipid nanoparticles with specific tumor targeting and cell-penetrating peptides was studied in vitro using human fibrosarcoma cells HT-1080. It was shown, that the binding of cell-penetrating peptide R7 – alone or combined with the peptide containing specific targeting motif NGR (Asn-Gly-Arg) – resulted in 3-fold decrease of Ce6 photoinduced activity as compared with that in nanoparticles without peptides (IC50 values were 0.7 μg/ml and 2.1 μg/ml, respectively). The NGR influence was unexpectedly low – less than 20% (IC50 1.7 μg/ml). This suggests the more importance of Ce6 cell penetration in this case, than of NGR-mediated targeting. The effect of inclusion of both peptides on the total cytotoxicity of Ce6 was minimal (10-16 times less than on the specific photoinduced activity). The obtained results – together with earlier shown effects on improvement of the pharmacokinetics of Ce6 in vivo after its embedding into phospholipid nanoparticles – indicate the prospects of using the obtained phospholipid nanoparticles system for photodynamic therapy.

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