El-Sahli, Sara2025-10-172025-10-172025-10-17http://hdl.handle.net/10393/50933https://doi.org/10.20381/ruor-31458Triple negative breast cancer (TNBC) is an aggressive form of breast cancer, that lacks targeting therapy, making chemotherapy the primary treatment option. However, chemotherapy leads to the enrichment of a subpopulation of cells with tumor initiating capacities called cancer stem cells (CSCs), that are implicated in treatment resistance, metastasis, and recurrence. To address this, I developed a triple-drug combination therapy targeting multiple aspects of tumorigenesis. Due to the limitation of conventional drug treatment, the use of nanoparticles (NPs) as a delivery system was introduced to increase therapeutic index. This triple-drug NPs suppressed bulk TNBC cells, CSC enrichment, and angiogenesis, both in vitro and in the clinically relevant patient-derived xenograft (PDX) model, paving the way for potential clinical application. RNA based therapeutics have emerged as a promising alternative in cancer treatment due to higher specificity in targeting key drivers of tumorigenesis. Using NPs as a delivery system, I showed the successful delivery of mRNA agents in PDX models, highlighting the promise of RNA-based NP therapies for overcoming limitations of conventional treatments in TNBC. As tumors are heterogenous with multiple drivers in play, I developed a NP-based co-delivery platform to deliver siRNA and mRNA for multitargeted gene regulation in cancer. These RNA-loaded NPs simultaneously knocked down and expressed target genes in TNBC in vitro and in vivo, highlighting their potential for multi-targeted therapy. Overall, throughout this thesis, using PDX models, I showed the effective delivery of both Drugs-NP and RNA- agents, laying the groundwork for future therapeutic strategies in TNBC treatment.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Breast CancerTNBCCancer Stem CellsNanoparticlesPDXThesis