Understanding Nanoparticle Transport Mechanisms in the Melanoma Microenvironment via a Tumor-on-a-Chip Approach

The MATRIx aims to develop a 3D melanoma tumor model on a chip (ToC) using patient-derived xenograft technology, which mimics the natural tumor microenvironment (TME) to enhance nanoparticle (NP) delivery to the tumor site and enable personalized treatment.In Western countries, melanoma is considered one of the most widespread cancers. Due to its aggressive nature and resistance to drugs, melanoma is the subject of extensive research aimed at creating more effective medications. The clinical translation of nanomedicine for cancer therapy has been hindered by a lack of knowledge regarding the TME, mechanisms of NP uptake and transfer, technical limitations for model implementation, and individual variations in phenotype. ToC modeling is an indispensable tool in cancer research providing a 3D dynamic environment with regulated fluid flow and shear stress, co-culturing, vascularization, easy operation and readout method, and time and cost saving in contrast to other cancer models. in addition, ToC provides high-throughput screening of nanomedicines, susceptibility, and resistance of cancer cells against drugs, allowing personalized therapy for patients with low cost and high reproducibility.Development of NPs based on patient’s melanoma TME response to active targeting NPs is the focus of MATRIx which will be implemented for the first time. My project's key deliverables will consist of identifying key players of TME around NP extravasation and enhancing NP retention at the tumor site. This initiative will aid in the development of more effective personalized cancer treatment strategies and will be of considerable interest to both academic and industrial sectors. MATRIx also fills my knowledge gaps. Following MATRIX conclusion, I will establish myself as a leader in the field of NP development, alongside tumor modeling on chip technology. I will receive advanced training skills to equip myself for conducting independent research and securing a permanent academic role.