Evaluation of Pd(II) Coumarin Complexes as Next-Generation Chemotherapeutics for Triple-Negative Breast Cancer Therapy Doctoral Project Description

Abstract

The research investigates the cytotoxicity, selectivity, and mechanisms of action of Pd(II) coumarin complexes on five Triple-Negative Breast Cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-468, MDA-MB-453, BT-549, and HCC-1187), the human breast adenocarcinoma cell line (MCF-7), and the non-tumorigenic control cell line (MCF-10A). The cells are treated with Pd(II) coumarin complexes (KL-19 and KL-20), their respective ligands (L-19 and L-20), cisplatin as a positive control, and culture medium containing 0.5% DMSO as a negative control. The initial phase of the project focuses on evaluating the dose-dependent effects and selectivity of these complexes. Preliminary experiments have shown promising antitumor activity, as evidenced by IC50 values, cell cycle analyses, and comparisons to cisplatin and the negative control. Additionally, the role of ligands versus the central ion in therapeutic efficacy is being explored. 

The project aims to identify and characterize the most active Pd(II) compounds, assess their anticancer mechanisms, and investigate their potential as targeted therapies for TNBC. Future work will expand on these findings by validating molecular targets, optimizing delivery methods such as liposome encapsulation, and advancing toward more physiologically relevant models, including organoids and patient-derived 3D cultures. If feasible, the project will extend to in vivo studies, evaluating therapeutic potential through tumor histology, proteomics, and biodistribution analyses using mass spectrometry. This research aspires to make a significant contribution to the fields of cancer research and drug development.

Planned milestones include the publication of key findings, collaborations with interdisciplinary teams, and the potential for developing targeted drug delivery systems. The project aligns with the broader goal of advancing cancer therapeutics through innovative bioengineering and nanomedicine approaches.