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Triple Negative Breast Cancer Preclinical Therapeutic Management by a Cationic Ruthenium-Based Nucleolipid Nanosystem
Maria Grazia Ferraro1, Marco Bocchetti2,3, Claudia Riccardi4
1BioChemLab, Department of Pharmacy, School of Medicine and Surgery, University of Naples "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
Abstract:
Based on compelling preclinical evidence concerning the progress of our novel ruthenium-based 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.
Insights
Novel ruthenium-based metallotherapeutics show promise for treating triple-negative breast cancer (TNBC). A nanoformulation, HoThyRu/DOTAP, effectively delivered an anticancer agent, inhibiting TNBC growth, proliferation, and metastasis.
Area of Science:
- Oncology
- Materials Science
- Nanotechnology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited treatment options and a poor prognosis, particularly affecting younger women, Black women, and those with BRCA1 mutations.
- Existing therapies for TNBC are often ineffective, highlighting a significant unmet medical need for novel therapeutic strategies.
- Ruthenium-based metallotherapeutics are emerging as promising alternatives to traditional platinum-based chemotherapy due to their distinct mechanisms of action.
Purpose of the Study:
- To evaluate the efficacy of a novel ruthenium(III) complex, AziRu, encapsulated in a biocompatible cationic liposomal nanoformulation (HoThyRu/DOTAP) for treating triple-negative breast cancer (TNBC).
- To explore the multimodal anticancer potential of HoThyRu/DOTAP, including its effects on TNBC cell growth, proliferation, migration, and invasion.
- To establish HoThyRu/DOTAP as a prospective candidate drug for TNBC, offering an alternative to platinum-based chemotherapy.
Main Methods:
- Utilized in vitro and in vivo experimental models of TNBC.
- Developed and characterized a biocompatible cationic liposomal nanoformulation (HoThyRu/DOTAP) for targeted delivery of the ruthenium(III) complex AziRu.
- Assessed the effects of HoThyRu/DOTAP on TNBC cell proliferation, migration, and invasion.
Main Results:
- The HoThyRu/DOTAP nanoformulation effectively delivered the antiproliferative AziRu complex in TNBC models.
- HoThyRu/DOTAP demonstrated multimodal anticancer activity by inhibiting TNBC cell growth, proliferation, migration, and invasion.
- Preclinical findings suggest that HoThyRu/DOTAP targets key pathways regulating invasive and migratory cancer phenotypes.
Conclusions:
- HoThyRu/DOTAP represents a promising nanostructured ruthenium complex for the treatment of metastatic TNBC.
- This metallotherapeutic offers a potential alternative to platinum-based drugs, addressing the unmet need in TNBC therapy.
- Further research into HoThyRu/DOTAP could lead to novel therapeutic strategies for challenging invasive neoplasms.
