Selectivity and efficacy towards target cancer cells, as well as biocompatibility, are current challenges of advanced chemotherapy powering the discovery of unconventional metal-based drugs and the search for novel therapeutic approaches. Among second-generation metal-based chemotherapeutics, ruthenium complexes have demonstrated promising anticancer activity coupled to minimal toxicity profiles and peculiar biochemical features. In this context, our research group has recently focused on a bioactive Ru(III) complex-named AziRu-incorporated into a suite of ad hoc designed nucleolipid nanosystems to ensure its chemical stability and delivery. Indeed, we proved that the structure and properties of decorated nucleolipids can have a major impact on the anticancer activity of the ruthenium core. Moving in this direction, here we describe a preclinical study performed by a mouse xenograft model of human breast cancer to establish safety and efficacy in vivo of a cationic Ru(III)-based nucleolipid formulation, named HoThyRu/DOTAP, endowed with superior antiproliferative activity. The results show a remarkable reduction in tumour with no evidence of animal suffering. Blood diagnostics, as well as biochemical analysis in both acute and chronic treated animal groups, demonstrate a good tolerability profile at the therapeutic regimen, with 100% of mice survival and no indication of toxicity. In addition, ruthenium plasma concentration analysis and tissue bioaccumulation were determined via appropriate sampling and ICP-MS analysis. Overall, this study supports both the efficacy of our Ru-containing nanosystem versus a human breast cancer model and its safety in vivo through well-tolerated animal biological responses, envisaging a possible forthcoming use in clinical trials.

Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium(III) complex with superior anticancer bioactivity / Piccolo, M.; Ferraro, M. G.; Raucci, F.; Riccardi, C.; Saviano, A.; Russo Krauss, I.; Trifuoggi, M.; Caraglia, M.; Paduano, L.; Montesarchio, D.; Maione, F.; Misso, G.; Santamaria, R.; Irace, C.. - In: CANCERS. - ISSN 2072-6694. - 13:20(2021), p. 5164. [10.3390/cancers13205164]

Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium(III) complex with superior anticancer bioactivity

M. Piccolo;M. G. Ferraro;F. Raucci;C. Riccardi;A. Saviano;I. Russo Krauss;M. Trifuoggi;L. Paduano;D. Montesarchio;F. Maione;R. Santamaria;C. Irace
Ultimo
Project Administration
2021

Abstract

Selectivity and efficacy towards target cancer cells, as well as biocompatibility, are current challenges of advanced chemotherapy powering the discovery of unconventional metal-based drugs and the search for novel therapeutic approaches. Among second-generation metal-based chemotherapeutics, ruthenium complexes have demonstrated promising anticancer activity coupled to minimal toxicity profiles and peculiar biochemical features. In this context, our research group has recently focused on a bioactive Ru(III) complex-named AziRu-incorporated into a suite of ad hoc designed nucleolipid nanosystems to ensure its chemical stability and delivery. Indeed, we proved that the structure and properties of decorated nucleolipids can have a major impact on the anticancer activity of the ruthenium core. Moving in this direction, here we describe a preclinical study performed by a mouse xenograft model of human breast cancer to establish safety and efficacy in vivo of a cationic Ru(III)-based nucleolipid formulation, named HoThyRu/DOTAP, endowed with superior antiproliferative activity. The results show a remarkable reduction in tumour with no evidence of animal suffering. Blood diagnostics, as well as biochemical analysis in both acute and chronic treated animal groups, demonstrate a good tolerability profile at the therapeutic regimen, with 100% of mice survival and no indication of toxicity. In addition, ruthenium plasma concentration analysis and tissue bioaccumulation were determined via appropriate sampling and ICP-MS analysis. Overall, this study supports both the efficacy of our Ru-containing nanosystem versus a human breast cancer model and its safety in vivo through well-tolerated animal biological responses, envisaging a possible forthcoming use in clinical trials.
2021
Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium(III) complex with superior anticancer bioactivity / Piccolo, M.; Ferraro, M. G.; Raucci, F.; Riccardi, C.; Saviano, A.; Russo Krauss, I.; Trifuoggi, M.; Caraglia, M.; Paduano, L.; Montesarchio, D.; Maione, F.; Misso, G.; Santamaria, R.; Irace, C.. - In: CANCERS. - ISSN 2072-6694. - 13:20(2021), p. 5164. [10.3390/cancers13205164]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/864992
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