On chip complex breast tumour microenvironment: Application to research in nanomedicine
Due to the COVID-19 crisis measures the PhD defence of Jean-Baptiste Blondé will take place online in the presence of an invited audience.
The PhD defence can be followed by a live stream.
Jean-Baptiste Blondé is a PhD student in the research group Applied Microfluidics for BioEngineering Research (AMBER). His supervisor is prof.dr.ir. S. le Gac from the Faculty of Electrical Engineering, Mathematics and Computer Science (EEMCS).
Cancer is the generic term used to describe a group of diseases related to abnormal cell growth leading to the formation of tumors, which disrupt the proper function of the organ they appear in. It is among the leading causes of death worldwide and which, due to the wide diversity of cancer types and the differences in progression between individuals, is also a challenging disease to cure. As an alternative to the currently established chemotherapeutic and radiotherapeutic treatments, the field of nanomedicine has in the last decades developed series of promising complex drugs by combining therapeutics agents with nanoparticle carriers. These “smart drugs”, known as nanomedicines, are able to selectively target the diseased tissue while transporting great quantities of active agents at low toxicity risks. Due to the complexity of nanomedicines, traditional 2D in vitro models have become however insufficient to fully characterize the potential of these new nanoscale drugs.
This thesis, entitled “On-chip complex breast tumor microenvironment: Application to research in nanomedicine”, makes use of alternative 3D in vitro models, to present a more relevant platform to investigate the efficacy of newly developed nanomedicines. This PhD research begins with cancer-only multicellular tumor spheroids (MCTS), which are some of the most common 3D in vitro models, by examining on how the spheroid size affects its protein expression profiles. The complexity of the model is next increased by first integrating fibroblasts in the MCTS, to investigate their impact on cellular organization, hypoxia formation, and extra-cellular matrix secretion, using different tissue clearing methods for possible 3D imaging. Next, a first tumor-on-chip platform is developed, by placing these MCTS models in a microfluidic chamber, to investigate the delivery of nanomedicines, and quantify their penetration inside the MCTS, through the use of fluorescently-labelled nanoparticles and high-resolution imaging, while varying several parameters (nanoparticle size, applied flow-rate and MCTS cellular composition). Finally, a “tumor microenvironment on chip” platform is proposed, complementing the MCTS with blood vessels, in which the delivery of intravenously injected nanomedicines could eventually be evaluated.