PhD defence T.B. (Timea) Gandek

Unravelling the tumour microenvironment: exploring nanotechnology for enhanced drug delivery and therapeutic efficacy

This dissertation focuses on the use of nanoparticles as drug delivery systems for cancer therapy, focusing on their interactions with cells and the tumour microenvironment. It explores the internalisation mechanisms and intracellular trafficking of liposomes and extracellular vesicles, identifying strategies to enhance therapeutic delivery while addressing common challenges in nanomedicine.

A key issue is achieving effective tissue penetration. This work evaluates the performance of extracellular vesicles in multicellular tumour spheroids composed of breast cancer cells and fibroblasts. The findings reveal that fibroblasts significantly promote EV uptake and distribution. Further studies examine the interactions between co-cultured fibroblasts and breast cancer cells, uncovering changes in extracellular matrix-related gene expression. These insights highlight potential targets to disrupt tumour stroma communication and inhibit cancer progression.

The research also investigates self-assembled DNA nanoflowers as multifunctional drug carriers responsive to radiotherapy cues. These nanostructures effectively encapsulate the chemotherapeutic doxorubicin and show efficient cellular uptake. However, their responsiveness to γ-radiation for controlled drug release was limited, indicating the need for further optimisation to fully harness their therapeutic potential.

In conclusion, this dissertation enhances our understanding of the biological mechanisms influencing nanoparticle-based drug delivery in cancer treatment. By addressing cellular uptake pathways and tumour microenvironment dynamics, it provides valuable insights to guide the development of more efficient and targeted therapeutic strategies.