Triple Negative Breast Cancer Preclinical Therapeutic Management by a Cationic Ruthenium-Based Nucleolipid Nanosystem

Sep 24, 2026

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Preclinical findings address invasive triple-negative breast cancer (TNBC), a malignancy affecting younger women, Black patients, and those with BRCA1 mutations, characterized by rapid growth, spread, limited options, and poor prognosis. The study uses an in vitro/in vivo TNBC model to evaluate a biocompatible cationic liposomal nanoformulation, HoThyRu/DOTAP, delivering the antiproliferative ruthenium(III) complex AziRu. Results show inhibition of TNBC growth, proliferation, migration, and invasion, supporting multitarget, multimodal anticancer activity and proposing alternative, non-platinum therapeutic directions.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages22

Reading Time55 min

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Abstract

Keywords

1. Introduction

Ru-based metallochemotherapeutics and Ru(II)/Ru(III) complexes

Article Triple Negative Breast Cancer Preclinical Therapeutic Management by a Cationic Ruthenium-Based Nucleolipid Nanosystem Maria Grazia Ferraro 1, Marco Bocchetti 2,3, Claudia Riccardi 4, Marco Trifuoggi 4, Luigi Paduano 4, Daniela Montesarchio 4, Gabriella Misso 3, Rita Santamaria 1,*, Marialuisa Piccolo 1, * and Carlo Irace 1 Citation: Ferraro, M.G.; Bocchetti, M.; Riccardi, C.; Trifuoggi, M.; Paduano, L.; Montesarchio, D.; Misso, G.; Santamaria, R.; Piccolo, M.; Irace, C. Triple Negative Breast Cancer Preclinical Therapeutic Management by a Cationic Ruthenium-Based Nucleolipid Nanosystem. Int. J. Mol. Sci. 2023, 24, 6473. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms24076473](10.3390/ijms24076473) Academic Editor: Ahmad R. Safa Received: 9 March 2023 Revised: 22 March 2023 Accepted: 28 March 2023 Published: 30 March 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 BioChemLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples “Federico II”, Via D. Montesano 49, 80131 Napoli, Italy; [mariagrazia.ferraro@unina.it](mariagrazia.ferraro@unina.it) (M.G.F.); [carlo.irace@unina.it](carlo.irace@unina.it) (C.I.) 2 Biogem Scarl, Institute of Genetic Research, Laboratory of Molecular and Precision Oncology, 83031 Ariano Irpino, Italy; [marco.bocchetti@unicampania.it](marco.bocchetti@unicampania.it) 3 Department of Precision Medicine, School of Medicine and Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; gabriella.misso@unicampania.it 4 Department of Chemical Sciences, University of Naples “Federico II”, Via Cintia 21, 80126 Napoli, Italy; [claudia.riccardi@unina.it](claudia.riccardi@unina.it) (C.R.); [marco.trifuoggi@unina.it](marco.trifuoggi@unina.it) (M.T.); [luigi.paduano@unina.it](luigi.paduano@unina.it) (L.P.) * Correspondence: rita.santamaria@unina.it (R.S.); [marialuisa.piccolo@unina.it](marialuisa.piccolo@unina.it) (M.P.) Abstract: Based on compelling preclinical evidence concerning the progress of our novel rutheniumbased metallotherapeutics, we are focusing research efforts on challenging indications for the treatment of invasive neoplasms such as the triple-negative breast cancer (TNBC). This malignancy mainly afﬂicts younger women, who are black, or who have a BRCA1 mutation. Because of faster growing and spreading, TNBC differs from other invasive breast cancers having fewer treatment options and worse prognosis, where existing therapies are mostly ineffective, resulting in a large unmet biomedical need. In this context, we beneﬁted from an experimental model of TNBC both in vitro and in vivo to explore the effects of a biocompatible cationic liposomal nanoformulation, named HoThyRu/DOTAP, able to effectively deliver the antiproliferative ruthenium(III) complex AziRu, thus resulting in a prospective candidate drug. As part of the multitargeting mechanisms featuring metal-based therapeutics other than platinum-containing agents, we herein validate the potential of HoThyRu/DOTAP liposomes to act as a multimodal anticancer agent through inhibition of TNBC cell growth and proliferation, as well as migration and invasion. The here-obtained preclinical ﬁndings suggest a potential targeting of the complex pathways network controlling invasive and migratory cancer phenotypes. Overall, in the ﬁeld of alternative chemotherapy to platinum-based drugs, these outcomes suggest prospective brand-new settings for the nanostructured AziRu complex to get promising goals for the treatment of metastatic TNBC. Keywords: ruthenium(III) complex; nucleolipid nanosystem; DOTAP liposome; triple-negative breast cancer (TNBC); pr

FAQs

What therapeutic system is studied for TNBC in this article?

The article evaluates HoThyRu/DOTAP, a biocompatible cationic liposomal nanoformulation designed to deliver the ruthenium(III) complex AziRu.

Why is triple-negative breast cancer considered challenging to treat?

TNBC tends to affect younger women, Black patients, and BRCA1 mutation carriers, and it grows and spreads faster than other breast cancers with fewer treatment options and worse prognosis.

What preclinical effects does HoThyRu/DOTAP show?

The study reports inhibition of TNBC cell growth and proliferation, along with reduced migration and invasion, indicating multimodal anticancer activity.

Sep 24, 2026

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