High spatial resolution imaging of cisplatin and Texas Red cisplatin in tumour spheroids using laser ablation isotope dilution inductively coupled plasma mass spectrometry and confocal fluorescence microscopy

Marković, Stefan; Uršič, Katja; Čemažar, Maja; Serša, Gregor; Starešinič, Barbara; Milačić, Radmila; Ščančar, Janez

doi:10.1016/j.aca.2021.338424

Cited by 16 publications

(13 citation statements)

References 37 publications

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“…We found that the highest cisplatin and DNP concentrations were detected in the outer layer of spheroids, while the drug amount decreased when approaching the spheroid core. This agrees with previously published data obtained using elemental imaging analysis 49 and LA-ICP-MS 13 for cisplatin and cisplatin-based compounds in spheroids.…”

supporting

confidence: 93%

“…Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) with pixel dimension of 2-10 μm has been used to demonstrate the concentration gradient of cisplatin in tumor spheroids in vitro and the preferential accumulation of cisplatin in necrotic regions of tumors in vivo. 12,13 Mass cytometry has facilitated the evaluation of Pt levels as low as 10 5 to 10 6 atoms per cell after a single intraperitoneal cisplatin administration using clinically relevant doses in mice xenograft model. 14 However, despite the high accuracy, these techniques require a complex sample preparation that often causes significant changes in the drug distribution.…”

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confidence: 99%

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In vitro/ In vivo Electrochemical Detection of Pt(II) Species

Vaneev

Gorelkin

Krasnovskaya

et al. 2021

Preprint

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The biodistribution of chemotherapy compounds within tumor tissue is one of the main challenges in the development of antineoplastic drugs, and novel techniques for simple, non-expensive, sensitive, and selective detection of various analytes in tumors are of great importance. In this paper we propose the use of platinized carbon nanoelectrodes (PtNE) for electrochemical detection of platinum-based drugs in various biological models, including single cells and tumor spheroids in vitro, and inside solid tumors in vivo. We have demonstrated quantitative direct detection of Pt(II) in breast adenocarcinoma MCF-7 cells treated with cisplatin and cisplatin-based DNP prodrug. To realize the potential of this technique in advanced tumor models, we measured Pt(II) in 3D tumor spheroids in vitro and tumor-bearing mice in vivo. The concentration gradient of Pt (II) species correlated with the distance from the sample surface in MCF-7 tumor spheroids. We then performed detection of Pt(II) species in tumor-bearing mice treated intravenously with cisplatin and DNP. We found that there was deeper penetration of DNP in comparison to cisplatin. This research demonstrates a novel minimally invasive, real-time electrochemical technique for the study of platinum-based drugs.

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supporting

confidence: 93%

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confidence: 99%

In vitro/ In vivo Electrochemical Detection of Pt(II) Species

Vaneev

Gorelkin

Krasnovskaya

et al. 2021

Preprint

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“…It is also important to note that our result of electrochemical Pt 2+ species detection in tumor spheroids is in good agreement with previously reported data obtained using LA–ICP–MS detection for cisplatin and cisplatin-based compounds in tumor spheroids. Marković et al have reported bioimaging of platinum in HT29 tumor spheroids treated with cisplatin using LA–ICP–MS . In cisplatin-treated tumor spheroids, platinum was localized primarily in the outer rim and to a lesser extent in the intermediary layer and the necrotic core of the spheroids.…”

Section: Resultsmentioning

confidence: 99%

“…Atom-based elemental imaging techniques, such as electron microscopy and X-ray microanalysis allows us to map the cellular distribution of platinum drugs. Also, laser ablation–ICP–MS (LA–ICP–MS) on tumor cell or tissue samples is a powerful widely used technique that can provide resolved analysis of elemental distribution within a sample. , Chang et al have reported a biodistribution of cisplatin in tumor and normal tissues using imaging mass cytometry . Greenhalgh et al have reported a distribution of platinum in cisplatin-treated non-small-cell lung cancer explant models .…”

Section: Introductionmentioning

confidence: 99%

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

et al. 2022

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We report herein the design, synthesis, and biological investigation of a series of novel Pt(IV) prodrugs with non-steroidal anti-inflammatory drugs naproxen, diclofenac, and flurbiprofen, as well as these with stearic acid in the axial position. Six Pt(IV) prodrugs 5–10 were designed, which showed superior antiproliferative activity compared to cisplatin as well as an ability to overcome tumor cell line resistance to cisplatin. By tuning the drug lipophilicity via variation of the axial ligands, the most potent Pt(IV) prodrug 7 was obtained, with an enhanced cellular accumulation of up to 153-fold that of cisplatin and nanomolar cytotoxicity both in 2D and 3D cell cultures. Pt2+ species were detected at different depths of MCF-7 spheroids after incubation with Pt(IV) prodrugs using a Pt-coated carbon nanoelectrode. Cisplatin accumulation in vivo in the murine mammary EMT6 tumor tissue of BALB/c mice after Pt(IV) prodrug injection was proved electrochemically as well. The drug tolerance study on BALB/c mice showed good tolerance of 7 in doses up to 8 mg/kg.

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“…Other studies that address the drug distribution within tumors are also needed. To date, a suitable method has been developed for the distribution of cisplatin [ 28 ]. In that study, high spatial resolution imaging of cisplatin distribution in spheroids of tumor cells was determined using two different approaches, namely, fluorescently labeled cisplatin determined by confocal fluorescence microscopy and laser ablation isotope dilution inductively coupled plasma mass spectrometry.…”

Section: Discussionmentioning

confidence: 99%

Bleomycin Concentration in Patients’ Plasma and Tumors after Electrochemotherapy. A Study from InspECT Group

et al. 2021

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The plasma concentration profile of bleomycin in the distribution phase of patients younger than 65 years is needed to determine the suitable time interval for efficient application of electric pulses during electrochemotherapy. Additionally, bleomycin concentrations in the treated tumors for effective tumor response are not known. In this study, the pharmacokinetic profile of bleomycin in the distribution phase in 12 patients younger than 65 years was determined. In 17 patients, the intratumoral bleomycin concentration was determined before the application of electric pulses. In younger patients, the pharmacokinetics of intravenously injected bleomycin demonstrated a faster plasma clearance rate than that in patients older than 65 years. This outcome might indicate that the lowering of the standard bleomycin dose of 15,000 IU/m2 with intravenous bleomycin injection for electrochemotherapy is not recommended in younger patients. Based on the plasma concentration data gathered, a time interval for electrochemotherapy of 5–15 min after bleomycin injection was determined. The median bleomycin concentration in tumors 8 min after bleomycin injection, at the time of electroporation, was 170 ng/g. Based on collected data, the reduction of the bleomycin dose is not recommended in younger patients; however, a shortened time interval for application of electric pulses in electrochemotherapy to 5–15 min after intravenous bleomycin injection should be considered.

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High spatial resolution imaging of cisplatin and Texas Red cisplatin in tumour spheroids using laser ablation isotope dilution inductively coupled plasma mass spectrometry and confocal fluorescence microscopy

Cited by 16 publications

References 37 publications

In vitro/ In vivo Electrochemical Detection of Pt(II) Species

In vitro/ In vivo Electrochemical Detection of Pt(II) Species

Pt(IV) Prodrugs with Non-Steroidal Anti-inflammatory Drugs in the Axial Position

Bleomycin Concentration in Patients’ Plasma and Tumors after Electrochemotherapy. A Study from InspECT Group

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