Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019

P. Heffeter; A. Riabtseva; Y. Senkiv; C. R. Kowol; W. Körner; U. Jungwith; N. Mitina; B. K. Keppler; T. Konstantinova; I. Yanchuk; R. Stoika; A. Zaichenko; W. Berger

doi:10.1166/jbn.2014.1763

Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019

P. Heffeter, A. Riabtseva, Y. Senkiv, C. R. Kowol, W. Körner, U. Jungwith, N. Mitina, B. K. Keppler, T. Konstantinova, I. Yanchuk, R. Stoika, A. Zaichenko, W. Berger

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26 Citations (SciVal)

Abstract

Ruthenium anticancer drugs belong to the most promising non-platinum anticancer metal compounds in clinical evaluation. However, although the clinical results are promising regarding both activity and very low adverse effects, the clinical application is currently hampered by the limited solubility and stability of the drug in aqueous solution. Here, we present a new nanoparticle formulation based on polymer-based micelles loaded with the anticancer lead ruthenium compound KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous solutions. Moreover, the nanoparticle formulation facilitated cellular accumulation of KP1019 (determined by ICP-MS measurements) resulting in significantly lowered IC₅₀ values. With regard to the mode of action, increased cell cycle arrest in G₂/M phase (PI-staining), DNA damage (Comet assay) as well as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were found in HCT116 cells treated with the new nanoformulation of KP1019. Summarizing, we present for the first time evidence that nanoformulation is a feasible strategy for improving the stability as well as activity of experimental anticancer ruthenium compounds.

Original language	English
Pages (from-to)	877-884
Number of pages	8
Journal	Journal of Biomedical Nanotechnology
Volume	10
Issue number	5
DOIs	https://doi.org/10.1166/jbn.2014.1763
Publication status	Published - 31 May 2014

Keywords

Anticancer cancer therapy
Cell death induction
Drug delivery
Nanocarrier
Ruthenium

ASJC Scopus subject areas

Bioengineering
Medicine (miscellaneous)
Biomedical Engineering
Materials Science(all)
Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1166/jbn.2014.1763

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Heffeter, P., Riabtseva, A., Senkiv, Y., Kowol, C. R., Körner, W., Jungwith, U., Mitina, N., Keppler, B. K., Konstantinova, T., Yanchuk, I., Stoika, R., Zaichenko, A., & Berger, W. (2014). Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019. Journal of Biomedical Nanotechnology, 10(5), 877-884. https://doi.org/10.1166/jbn.2014.1763

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abstract = "Ruthenium anticancer drugs belong to the most promising non-platinum anticancer metal compounds in clinical evaluation. However, although the clinical results are promising regarding both activity and very low adverse effects, the clinical application is currently hampered by the limited solubility and stability of the drug in aqueous solution. Here, we present a new nanoparticle formulation based on polymer-based micelles loaded with the anticancer lead ruthenium compound KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous solutions. Moreover, the nanoparticle formulation facilitated cellular accumulation of KP1019 (determined by ICP-MS measurements) resulting in significantly lowered IC50 values. With regard to the mode of action, increased cell cycle arrest in G2/M phase (PI-staining), DNA damage (Comet assay) as well as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were found in HCT116 cells treated with the new nanoformulation of KP1019. Summarizing, we present for the first time evidence that nanoformulation is a feasible strategy for improving the stability as well as activity of experimental anticancer ruthenium compounds.",

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AU - Heffeter, P.

AU - Riabtseva, A.

AU - Senkiv, Y.

AU - Kowol, C. R.

AU - Körner, W.

AU - Jungwith, U.

AU - Mitina, N.

AU - Keppler, B. K.

AU - Konstantinova, T.

AU - Yanchuk, I.

AU - Stoika, R.

AU - Zaichenko, A.

AU - Berger, W.

PY - 2014/5/31

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AB - Ruthenium anticancer drugs belong to the most promising non-platinum anticancer metal compounds in clinical evaluation. However, although the clinical results are promising regarding both activity and very low adverse effects, the clinical application is currently hampered by the limited solubility and stability of the drug in aqueous solution. Here, we present a new nanoparticle formulation based on polymer-based micelles loaded with the anticancer lead ruthenium compound KP1019. Nanoprepared KP1019 was characterised by enhanced stability in aqueous solutions. Moreover, the nanoparticle formulation facilitated cellular accumulation of KP1019 (determined by ICP-MS measurements) resulting in significantly lowered IC50 values. With regard to the mode of action, increased cell cycle arrest in G2/M phase (PI-staining), DNA damage (Comet assay) as well as enhanced levels of apoptotic cell death (caspase 7 and PARP cleavage) were found in HCT116 cells treated with the new nanoformulation of KP1019. Summarizing, we present for the first time evidence that nanoformulation is a feasible strategy for improving the stability as well as activity of experimental anticancer ruthenium compounds.

KW - Anticancer cancer therapy

KW - Cell death induction

KW - Drug delivery

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Nanoformulation improves activity of the (pre)clinical anticancer ruthenium complex KP1019

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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