Date: Friday, December 8, 2017
Time: 12:00pm - 1:00pm
Speaker: Michael Strano, Ph.D., Carbon P. Dubbs Professor of Chemical Engineering
Affiliation: Department of Chemical Engineering, MIT
Talk Title: Applications of Nanosensors to Understanding Biochemical Signaling Within the Human Body
Abstract: The human body is a vast network of biochemical signaling pathways dictating physiological and pathological processes. To probe this network, our research group has introduced Corona Phase Molecular Recognition, or CoPhMoRe, for discovering synthetic, heteropolymer corona phases that form molecular recognition sites at the nanoparticle interface. By screening libraries of synthetic heteropolymers chemically adsorbed onto single-walled carbon nanotubes (SWNT), we have engineered new optical biosensors that exhibit highly selective recognition for specific molecules, including riboflavin, L-thyroxine, dopamine, nitric oxide, sugar alcohols, estradiol, as well as proteins such as fibrinogen. The results have significant potential in that nanoparticles such as SWNT can be interfaced to biological systems at the sub-cellular level, allowing monitoring of sub-cellular, cellular, tissue, and whole-organism processes. With deep tissue penetration, we demonstrated our nanosensors in vitro with no photobleaching, and in vivo with no fluorescence degradation (400+ days).
Engineering the nanoparticle corona in this way offers significant potential to translate sensor technology to previously inaccessible environments. We have measured dopamine efflux from PC12 cells, which may allow monitoring of neuroendocrine production and signaling. Additionally, we have synthesized selective cortisol and progesterone sensors and are currently performing in vivo measurements of progesterone in mice. Cortisol has been implicated in numerous pathological conditions, including depression, post-traumatic stress disorder, bipolar disorder, and autism, whereas progesterone is the primary female sex hormone dictating fertility. Monitoring these, as well as other steroid hormones, could provide significant insight about the etiology of various endocrine-related pathologies. In the diabetes space, we have synthesized an insulin sensor and are currently designing glucose responsive insulins (GRI). Interfacing insulin sensors and a GRI with currently available continuous glucose monitors may revolutionize diabetes treatment, as insulin dosages will be more tightly controlled in a closed loop fashion. Last, I will discuss our current work in cancer. One major challenge in cancer is the ability to have an accurate and comprehensive picture of the intratumoral delivery and localization of chemotherapeutic drugs. The tumor heterogeneity has a significant impact on drug delivery, drug uptake, and therapeutic effectiveness. Our nanosensor platform can provide real-time spatiotemporal information about tumor metabolites and chemotherapeutic drug delivery. This feedback will give physicians and patients information about the tumor molecular response significantly earlier in a matter of hours or days compared to the weeks or months needed to see measurable size changes on CT or MRI.