Designing novel multifunctional nanosystems to improve intracellular delivery

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The growing interest in applying nanotechnology to medicine, nanomedicine, is due to its appealing features in drug delivery, diagnosis, and imaging. Nanotechnology-based drug delivery platforms (nanoparticles, NPs) are typically in 1-100 nm range, capable of encapsulating thousands of therapeutic and/or imaging agents inside their nanostructures and delivering them directly to the disease sites, enhancing their therapeutic effects and minimizing unwanted toxicities. Despite significant enthusiasm and investment, the field has not yet reached its full potential, as only ~17 nanomedicines have been approved for clinical use in Europe and North America. Several issues, such as optimizing the biophysiochemical properties of NPs, gaining the fundamental understanding of nano-bio interactions, and improving the intracellular delivery of therapeutic agents, need to be addressed to maximize the potential of nanotechnology applications in healthcare. The long-term vision of our research program is to develop a fundamental framework for rationally designing and developing NPs for site-specific delivery, overcoming a variety of biological barriers to reach desired sites, identifying optimal NP dose ranges to achieve maximum effect, and minimizing adverse effects induced by the nanomaterials themselves. To this end, my research program is centred around two main interconnected themes: the design and synthesis of advanced multifunctional NP platforms for improved intracellular delivery of a variety of agents; and the exploration of their interactions with blood, tissue, cellular and intracellular components in vitro and in vivo settings. The short-term objective of the proposed research program is to gain a detailed understanding of nano-bio interactions of redox-responsive NPs with intracellular components in the context of NPs' intracellular trafficking and payload delivery. Our aims are 1) Develop novel redox-responsive NPs for nucleotides delivery. 2) Study the impact of NP's interactions with endosomal-lysosomal components on intracellular trafficking and delivery in biological settings. The long-term goal is to incorporate the knowledge gained from these studies into a feedback loop to develop next-generation NPs. The outcome of my research program will provide guidelines for rationally designing potent nanoparticle-based drug delivery systems and thus advancing the nanomedicine research field. Most importantly, highly qualified personnel trained in this research program will learn various experimental and analytical skills in chemistry, engineering, and biology. Additionally, they will also benefit from a robust interdisciplinary environment and gain valuable research experience equipping them for careers in both industry and academia.