Engineering Cooperative Nanosytems

Abstract

Our laboratory is interested in engineering tools and systems using nanoparticle scaffolds to transform the diagnosis and treatment of cancer. We aim to integrate nanomaterials with enhanced nanoscale properties and bioresponsive functionalities with our knowledge of the tumor microenvironment to explore this paradigm. Towards this end, we have developed and investigated nanoparticle conjugates based on three nanoparticle cores that harness features of the nanoscale: semiconductor quantum dots that exhibit size-based optical properties, dextran-coated iron oxide particles whose assembly alters the spin-spin relaxation time of hydrogen protons on magnetic resonance imaging, and polymer-coated gold nanorods that interact resonantly with near-infrared light. Our studies have shown how these nanoparticles specifically designed to enhance their interaction with the biological environment can help achieve targeting, triggered self-assembly, remote actuation with radiofrequency fields, sensing of kinase activity, and delivery of short interfering RNAs. In collaboration with Erkki Ruoslahti (Burnham Institute), we have explored how decorating the surface with peptides obtained from in vivo phage display can alter the properties of these nanoparticles and control their trafficking. To increase the accumulation of the nanoparticles at the tumor site we are exploring in vivo self-assembly of these particles. Our approach is inspired by platelets_natural microparticles that normally circulate in a latent form but can home to sites of injury and transform to an activated state, whereby they adhere and recruit more platelets. This results in assemblies of magnetic nanoparticles that may then acquire emergent properties, allowing either their enhanced visualization or remote actuation of drug delivery. More recently, we have also emulated biological systems where biological components remotely communicate via biological intermediates. The resultant nanoparticle formulations then act as a “system” to produce emergent behaviors for enhancing diagnosis and therapy.