Carolina Sato De Oliveira

According to a recent study by the International Agency for Research on Cancer, 1 in 5 people will develop cancer at some point during their lifetime. Conventional cancer therapies such as surgery, radiotherapy, or chemotherapy often fall short due to the incomplete removal of cancerous tissue, the development of multidrug resistance, or the non-specificity of the therapy. Current therapeutical approaches aim to develop safe, selective, and efficient treatment strategies for difficult-to-cure cancers. Recently, phototherapies, such as photothermal (PTT) and photodynamic therapy (PDT), have demonstrated promising potential in preclinical cancer studies. These therapies aim to selectively destroy cancerous tissue through localized photothermal and photochemical processes. However, in traditional approaches, they can be invasive to the human body, primarily because the materials used lack specificity for cancer cells. The development of nanomaterials marks a significant step forward in phototherapies of cancers. Nanoparticles smaller than 200 nm accumulate in the tumour tissue and exhibit strong absorption in the near-infrared range, improving the selectivity and efficiency of light-mediated treatments, and ultimately drastically enhancing their outcomes. Nanomaterial-mediated phototherapies have reached clinical trials but knowledge concerning the efficiency, mechanism and toxicity of this therapy remains limited. This project aims to unravel the mechanisms involved in nanomaterial-mediated phototherapies on a single-cell level and investigate cellular responses to phototherapies. Fluorescence-based sensors and advanced microscopy techniques will be used to monitor temperature, reactive oxygen species (ROS) generation, and cellular stress activity, enabling us to map stress-response signalling and its spread within cells. To mimic the physiological features present in solid tumors most accurately, advanced tumor models will be used. 3D cell models such as spheroids, are more accurate representations of the heterogeneity and complexity of in vivo tumors compared to traditional cell monolayers and can provide better insights into the signalling pathways involved in the response to phototherapies. Overall, the goal of this project is to provide valuable insights into the interaction between NPs and cancer cells in solid tumors, for the development of more effective strategies for nanoparticle-based cancer therapies.