Nanoformulations of a Potent copper-based Aquaporin Inhibitor With Cytotoxic Effect Against Cancer Cells

Nave, Mariana; Castro, Rui E.; Rodrigues, Cecília M. P.; Casini, Angela; Soveral, Graça; Gaspar, Maria Manuela

doi:10.2217/nnm-2016-0086

Cited by 49 publications

(54 citation statements)

References 62 publications

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“…In our previous work [30], the Cu 2+ complex, Cuphen [Cu(phen)Cl2] (Figure 1), was successfully incorporated in long circulating nanoliposomes, demonstrating antiproliferative effects towards different tumour cell lines and absence of in vivo toxicity after parenteral administration in healthy mice [30]. In the present study, we designed Cuphen long circulating nanoliposomes and tested their therapeutic effect in a syngeneic murine melanoma model, following an optimization of experimental conditions.…”

Section: Introductionmentioning

confidence: 91%

“…Nanoliposomes composed of the selected phospholipids were prepared by the dehydrationrehydration method [30,31]. Long circulating nanoliposomes were produced by including DSPE-PEG.…”

Section: Nanoliposomes Preparationmentioning

confidence: 99%

“…Loading capacity was defined as the final Cuphen to lipid ratio (Cuphen/Lip)f and the incorporation efficiency (I.E.) in percentage was determined according to the following formula: Cuphen was quantified spectrophotometrically at 270 nm ( = 33,000 M -1 cm -1 ) after disruption of the nanoliposomes with ethanol [30]. Linearity of calibration curves was ensured from 2.5 to 25 μM (R² = 0.9997; Slope: 0.0309 ± 0.0002; Y-intercept [x = 0]: -0.0078 ± 0.0010).…”

Section: Nanoliposomes Characterizationmentioning

confidence: 99%

“…B16F10 murine melanoma cell viability was evaluated in the absence (control) or presence of increasing concentrations of Cuphen, in free and liposomal forms, by the MTS assay [30].…”

Section: Cytotoxicity Evaluationmentioning

confidence: 99%

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Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

Pinho

Amaral

Castro

et al. 2019

Nanomedicine (Lond.)

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Aim: Preclinical evaluation of a cytotoxic copper (II) complex formulated in long circulating nanoliposomes for melanoma treatment. Materials & methods: Liposomal nanoformulations of the copper complex were characterized in terms of thermodynamic behavior (differential scanning calorimeter), pH-sensitivity (spectrophotometry) and antiproliferative effects against murine melanoma B16F10 cells in vitro. Preclinical studies were performed in a C57BL/6 syngeneic melanoma model. Results: Nanoformulations were thermodynamically stable, and CHEMS-containing nanoliposomes were pH-sensitive and preserved the antiproliferative properties of the copper compound. These nanoformulations significantly impaired tumor progression in vivo, devoid of toxic side effects, compared with control mice or mice treated with the free metallodrug. Conclusion: Copper complex-containing nanoliposomes demonstrate high anticancer efficacy and safety, constituting a step forward to the development of more effective therapeutic strategies against melanoma.

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Section: Introductionmentioning

confidence: 91%

“…Nanoliposomes composed of the selected phospholipids were prepared by the dehydrationrehydration method [30,31]. Long circulating nanoliposomes were produced by including DSPE-PEG.…”

Section: Nanoliposomes Preparationmentioning

confidence: 99%

Section: Nanoliposomes Characterizationmentioning

confidence: 99%

“…B16F10 murine melanoma cell viability was evaluated in the absence (control) or presence of increasing concentrations of Cuphen, in free and liposomal forms, by the MTS assay [30].…”

Section: Cytotoxicity Evaluationmentioning

confidence: 99%

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Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

Pinho

Amaral

Castro

et al. 2019

Nanomedicine (Lond.)

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“…lipoplatin), [304] iron [305] and copper complexes. [306] Such type of drug delivery systems are ideal to reduce metal speciation and should find more applications in the future at the earliest stage of the metallodrug development process.…”

Section: Discussionmentioning

confidence: 99%

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

Wenzel

Casini

2017

Coordination Chemistry Reviews

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102

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Metal-based compounds form a promising class of therapeutic agents, whose mechanisms of action still need to be elucidated, and that are in general prone to undergo extensive speciation in physiological environment. Thus, determination of the fate of the metal compounds in complex biological systems, contributing to their overall pharmacological and toxicological profiles, is important to develop more rationalised and targeted metal-based drugs. To these aims, a number of spectroscopic and biophysical methods, as well as analytical techniques, are nowadays extensively applied to study the reactivity of metal complexes with different biomolecules (e.g. nucleic acids, proteins, buffer components). Among the various techniques, molecular mass spectrometry (MS) has emerged in the last decade as a major tool to characterise the interactions of metallodrugs at a molecular level. In this review, we present an overview of the information available on the reactivity of various families of therapeutic metallodrugs (mainly anticancer compounds based on Pt, Ru, Au and As) with biomolecules studied by different MS techniques, including high-resolution ESI-, MALDI-and ion mobility-MS among others. Representative examples on the potential of the MS approach to study non-covalent interactions are also discussed. The review is organized to present results obtained on samples with different degrees of complexity, from the interactions of metal compounds with small model nucleophiles (amino acids and nucleobases), model peptides/oligonucleotides, target proteins/nucleic acids, to the analysis of serum, cell extracts and tissue samples. The latter requiring combination of proteomic methods with advanced MS techniques. Correlations between molecular reactivity of metallodrugs and biological activity are hard to establish, but differences in the reactivity of metallodrugs to biomolecules and their different adducts, as revealed by MS methods, may indicate differences in their modes of action. Overall, the knowledge offered by MS methods on metallodrugs speciation is invaluable to establish new rules and define new trends in the periodic table aimed at rationalizing the behavior of metal compounds in complex living systems. Keywordsmetal-based drugs; proteins; nucleic acids; mass spectrometry; metallomics. Corresponding Author Angela Casini Corresponding Author's InstitutionCardiff University To view all the submission files, including those not included in the PDF, click on the manuscript title on your EVISE Homepage, then click 'Download zip file'. Order of Authors 1 Answers to Reviewers Reviewer 1 The authors have made some effort to answer suggestions and the manuscript is improved. Since it is a review, there is, strictly, no new information but nevertheless the compilation of data and references could be useful.Answer: no further comments. Liu et al." in place of "Lu et al." iv) Some symbols in the PDF file are not correctly displayed. Reviewer Answer:We have inserted all the minor modifications requested by this rev...

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Encyclopedia of Inorganic and Bioinorganic Chemistry

Giansiracusa

Gransbury²,

Chilton

et al. 2012

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Single-Molecule Magnets (SMMs) are finite molecular species that display slow relaxation of their magnetisation, equivalent to a magnetic memory effect. Here we give an overview of how SMM behaviour can arise from the spin properties of a giant molecular spin or unpaired electrons on a single metal centre. We outline the criteria for obtaining SMM properties, and how these have developed through theoretical insight to lead to the rapid advancement of SMM performance. We discuss the progression of the field from the original Mn12 polymetallic cluster, to carefully engineered coordination complexes of Ln ions. Classes of compounds discussed include 3d, 3d-4f and 4f polymetallic clusters, 3d and 4f monometallic complexes, and homo-and hetero-metallic exchange-coupled SMMs, including those bridged by radical ligands and/or encapsulated in endohedral fullerenes. The state-ofthe-art in SMMs is discussed, leaving the reader with an up-to-date understanding of theory and synthetic design, with references to comprehensive reviews.For readers new or returning to the area, we highlight the standard experiments used to characterise SMMs -including magnetic hysteresis, zero-field cooled/field cooled magnetic susceptibility, alternating current susceptibility and magnetisation decay measurements. We highlight the common pitfalls often encountered in the literature in measurements, data analysis and structural correlation of properties. We aim to provide a clear background for relaxation mechanisms in SMMs and the quantification of performance using energy barriers, blocking temperatures and relaxation rate. The reader is directed towards a series of proof-ofconcept publications which have spearheaded the implementation of SMMs towards future applications in high density data storage, quantum information processing and spintronics.

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Nanoformulations of a Potent copper-based Aquaporin Inhibitor With Cytotoxic Effect Against Cancer Cells

Cited by 49 publications

References 62 publications

Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

Copper Complex Nanoformulations Featuring Highly Promising Therapeutic Potential in Murine Melanoma Models

Mass spectrometry as a powerful tool to study therapeutic metallodrugs speciation mechanisms: Current frontiers and perspectives

Encyclopedia of Inorganic and Bioinorganic Chemistry

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