Cancer targeting nanoparticles face a variety of biological environments between the site of injection and cancer cells. While researchers can measure the properties of nanoparticles outside the body, interactions with biological environment and its effect on nanoparticle tumour delivery remains unexplored. Understanding these barriers for cancer nanomedicine is the first step towards overcoming them. Here, I focus on three aspects of 3 nano-bio interactions enroute to cancer that dictates its biological fate: 1) Nanoparticle-Blood: Serum protein adsorption on circulating nanoparticles can be used as input to develop a supervised learning algorithm that can predict the fate of nanoparticles. This model achieved 77-95% accuracy in its prediction and altering the proteins on the surface led to reduction in liver and spleen uptake. 2) Nanoparticle – Tumour Blood Vessels: The dominant mechanism of nanoparticle entry into solid tumours is trans-endothelial and not through inter-endothelial gaps via Enhanced Permeation and Retention (EPR) effect. Upto 97% of nanoparticles were found to extravasate into the tumour via trans-endothelial pathways. This changes our approach to developing cancer nanomedicine as we now have to utilize this active mechanism instead of relying of passive accumulation. 3) Nanoparticle-Tumour: We have developed an approach that allows 3D imaging of nanoparticles in intact tumours. This technique is high throughput, cost effective and is compatible with both organic and inorganic nanoparticles. This is now allowing us to map all the barriers to cancer nanomedicine in tumours. This map is powerful because it forms the basis for classifying tumours into zones of varying nanoparticle distribution and can make accurate predictions of nanoparticle targeting efficiency. The work presented here arms the field of cancer nanomedicine with the biological barriers that need to be taken into design considerations to improve its clinical translation.Ph.D.2020-12-09 00:00:0
