In Vivo Imaging Guides Prediction and Optimization of Nanomedicine Action in Cancer

Dr. Miles Miller

Assistant Professor of Radiology, MGH

Drug-loaded therapeutic nanoparticles have been developed to deliver drugs more safely and effectively to tumors.  In principle, the “enhanced permeability and retention” (EPR) effect operates to improve selective tumoral nanomedicine delivery via features including hyper-permeable tumor vasculature and dysfunctional lymphatics; however, in practice, EPR effects are often heterogeneous across tumors and patients, and consequently have been difficult to reliably exploit in the clinic. Imaging of nanomedicine delivery, using techniques such as time-lapse intravital microscopy and ex vivo tissue clearing, offer insights into how nanomedicines behave in the tumor microenvironment and what factors limit their efficacy. Results have pointed towards new translational strategies for patient selection and synergistic drug combinations.

Miles Miller received his A.B. in Chemistry from Princeton University, and his Ph.D. in Biological Engineering from the Massachusetts Institute of Technology (Advisors: Douglas Lauffenburger and Linda Griffith). He trained as a NIH postdoctoral fellow under Dr. Ralph Weissleder at MGH. He specializes in parsing mechanisms of cell signaling and drug action from a quantitative network-level perspective, with training in computational modeling, imaging, nanotechnology, cell signaling biology, and drug delivery. His lab The lab uses computational and experimental methods to understand how mammalian cell signaling and regulation integrate across multiple scales, from the molecular to whole-body level. We combine multiplexed measurements with in vivo imaging and systems-level mathematical modeling to distill principles of cellular communication. He particularly focuses on inflammation and cancer, where abnormal signals in multiple cell types promote disease progression and are therapeutically targeted.