2018 Annual Symposium Speaker Abstracts
Dr. Chad A. Mirkin
“Rational Vaccinology: In Pursuit of the Perfect Vaccine”
Spherical Nucleic Acids (SNAs) are an emergent therapeutic architecture, which consist of oligonucleotides radially conjugated to a nanoparticle core. This arrangement of DNA or RNA gives rise to unique properties not observed with their linear counterparts, such as rapid cellular uptake and increased resistance to nuclease degradation. The emergent properties of SNAs are revolutionizing the way we study, track, and treat disease and may help realize the promise of rational vaccinology: elucidating and leveraging the structure-activity relationships of SNAs to arrive at the most potent immunostimulatory construct. We are advancing this vision forward by treating solid tumors with immunostimulatory SNAs that activate an immune response against cancer cells. This presentation will describe these advancements and illustrate how rational vaccinology can improve human lives.
Adaptable Biomaterials for Combination Cancer Therapy
Systemic delivery of drugs is the preferred therapeutic approach for the treatment of many types of cancers, especially to downstage the disease prior to resection, or as an adjuvant following resection. However, only about 1% of the administered conventional drug delivery systems get to the tumor site, with no ability to discriminate between cancer and normal cells, leading to significant adverse outcomes. I will describe the combination of the systemic delivery of the nanoparticles with local delivery to improve outcomes; the latter achieved by crosslinking of the nanoparticles to form an injectable adhesive hydrogel and releases therapeutics in a controlled- and selective-manner, to enhance tumour shrinkage and prevent recurrence, in a colon cancer model. I will review the design of nanoparticles for the treatment of solid tumors that can provide selective drug uptake in cancer cells while leaving healthy cells intact. I will discuss the benefits of multimodal combination therapy—drug release, gene therapy, and thermal ablation— in the treatment of solid tumors. New therapeutic strategies for cancer therapy and the employment of diverse administration routes will provide the scientific, pharmaceutical and clinical communities with unprecedented opportunities for the development of new clinically-relevant cancer therapies.
Dr. Keith A. Brown
“Reading, Writing, and Learning at the Nanoscale with Scanning Probes”
Polymers are excellent candidates for materials-by-design as advances in chemistry have yielded vast libraries of polymer materials that can be prepared or blended to achieve a wide array of properties. While approaches for preparing and studying polymers at the bulk scale are reasonably well established, it is much more challenging to interrogate polymers at the nanoscale, dramatically slowing the generation of new knowledge. Here, we discuss how scanning probes can provide new insight in the study of soft materials by interrogating and synthesizing polymer structures at the nanoscale. Initially, we will explore how polymer nanomechanics can be elucidated by atomic force microscopy. In particular, we have recently found that glassy polymers become softer when confined in thin films while elastomers become stiffer when confined. Aside from having implications for the utilization of polymers at the nanoscale, these observations highlight the care needed to quantitatively measure properties of nanoscale samples. In addition to measuring properties, scanning probes can also define arrangements of soft materials at the nanoscale. To explore this, we present recent progress in the development of a closed-loop system to pattern structures wherein real-time feedback is leveraged to observe transport of material from the tip of a probe to a surface. Finally, having a single tool that can both write and interrogate materials at the nanoscale raises fascinating possibilities as it could potentially be used as an autonomous system to uncover knowledge about nanoscale polymers. To explore these opportunities, we highlight recent work combining autonomous experimentation, machine learning, and additive manufacturing. Collectively, this work highlights the open questions and challenges inherent to understanding nanoscale soft systems and shows how scanning probes can provide a unique platform for answering these questions.
Dr. Daniel A. Heller
“Nanomedicines to Improve Precision Medicines”
Therapy based on personalized medicine—the genomic context of a patient’s disease—has become a leading strategy to treat cancer. Small molecule drugs such as kinase inhibitors, which target key effectors of cancer signaling pathways, constitute a major component of this strategy. However, such drugs can affect the same signaling pathways in healthy tissues, which often leads to dose-limiting toxicity (on-pathway toxicity), while imperfect selectivity for the therapeutic target can also limit dosing (off-pathway toxicity). In addition, the anti-tumor effects of kinase inhibitors are often diminished by the activation of compensatory or parallel pathways as a mechanism of resistance. Increasing the therapeutic index of targeted therapies, used as monotherapies or combinations, would greatly improve their effectiveness. My laboratory is developing nanomedicine platforms to obviate dose-limiting toxicities kinase inhibitors and thereby improve therapeutic index in solid tumors. One such platform targets P-selectin on tumor vasculature. P-selectin is expressed endogenously in certain tumors, and it can be greatly induced by ionizing radiation. Our data shows improved efficacy of MEK and PI3K inhibitors and the abrogation of dose-limiting toxicities, such as skin rash and hyperglycemia, to improve therapeutic index. The nanoparticles also resulted in prolonged inhibition of the drug targets in tumor tissues, constituting a significant modulation of the kinase inhibitor pharmacologic properties.
Dr. Chen Yang
“Discover and Design Functional Nanomaterials for Biomedical Applications”
The mission of our research is developing new nanomaterials with functionality gained from low dimensionality, structural and compositional complexity, and novel optical, chemical, and electrical properties of nanostructures and for great societal impact. One of our current focus is on new active functional biomaterials that modulate living biological systems, beyond passive imaging and recording. The significance of such development is that the active modulation through novel materials offers tools for fundamental studies and more significantly, deliver potential translational outcomes for treatments. Specifically, recent development on active nanomaterials for neuron regeneration and stimulation will be discussed.