Frontiers in Nanotechnology Seminar Series – André Nel
Distinguished Professor of Medicine
Research Director, California Nanosystems Institute
University of California, Las Angeles (UCLA)
Nano-enabled Chemotherapy and Chemo-immunotherapy for Pancreas and Solid Cancers
Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is currently treated by two major drug regimens, namely gemcitabine, and a 4-drug combination known as FOLFIRINOX (oxaliplatin, 5-fluorouracil,
irinotecan, and leucovorin). In addition to the impediments of late diagnosis and early metastatic spread, a major treatment obstacle is the abundant dysplastic stroma, which provides a barrier to vascular access of
chemotherapeutic agents at the tumor site as well as participating in drug resistance and a compromised immune response. While FOLFIRINOX leads to better survival outcome, the high toxicity levels of irinotecan and oxaliplatin prevent their use as first-line treatment options. Nel and his colleagues have developed a mesoporous silica nanoparticle (MSNP) carrier, coated by a lipid bilayer, which can effectively deliver (i) a synergistic combination of paclitaxel and gemcitabine, or (ii) irinotecan as a single drug. These “silicasome” carriers outperform commercial nanocarriers (Abraxane and Onivyde) in terms of efficacy as well as toxicity reduction in a rigorous orthotopic PDAC model. For example, the irinotecan carrier significantly
reduces bone marrow and gastrointestinal toxicity compared to Onyvide. In addition to survival improvement by chemotherapy delivery, Nel’s researchers have also developed a nano-enabled immunotherapy platform
for PDAC and other solid cancers (e.g., breast cancer) that is premised on the induction of immunogenic cell death (ICD) plus local delivery of a metabolic checkpoint inhibitor. A series of nanocarriers have now been developed for successful tumor killing at primary and metastatic cancer sites. Researchers can also achieve ICD outcomes with catalytically active nanomaterials that induce the biological response pathways that culminate in the specialized form of cell death, concomitant with the ability to activate innate immune responses to provide effective immunotherapy outcomes.
Dr. Nel is a Distinguished Professor of Medicine at UCLA, where he has successfully established one of the largest federally-funded nanotechnology research programs in the US. The UC Center for the Environmental Implications of Nanotechnology is the premier think tank for the safe and sustainable implementation of nanotechnology in the US, while the team-based science efforts he has put together as Research Director of the California Nanosystems Institute is spearheading nano medicine translation and commercialization on the UCLA campus. Professor Nel is a recipient of the Harry Truman Award and received the 2013 California
Governor’s Environmental Economic Leadership Award. He plays national leadership roles in science, biomedical research, nanotechnology, and policy. He served as a chair of an NIH study section and was an NSF panel member for producing a comprehensive US Government blueprint to further develop
the Nanotechnology Initiative (NNI) from 2010-2020. He was a member of the US Bilateral Presidential Commission for technology cooperation with Russia, and served as a panel member on Pres. Obama’s PCAST panel for strategizing the NNI technological innovation and commercialization. Dr. Nel has represented the US State Department and the NIH in cooperative research agreements with Japan and the Chinese Academy of Sciences, in which he was elected as Honorary Foreign Professor. In addition to groundbreaking work in nanotechnology, Dr. Nel co-directed a leading EPA Particle Center studying the impact of air pollution on asthma. He was PI of the NIH-funded UCLA Asthma Center and received the John Salvaggio Award
for outstanding service to the American Academy of Asthma, Allergy and Immunology. He is a frequently invited plenary speaker at international multidisciplinary science conferences, a highly cited scientific scholar, and inventor contributing patents that spearheaded a startup company.