BME Seminar Series: Natalie Artzi, Ph.D.
Thursday, March 5, 2015
Goergen Hall 101 (Sloan Auditorium)
"Mechanistic Understanding of Materials Performance in Complex Biological Environments as a Tool for Translation"
Natalie Artzi, Ph.D.
Department of Anesthesiology
Brigham and Women's Hospital, Harvard Medical School
Institute for Medical Engineering and Science, MIT
Abstract: Personalized medicine, as originally conceived, was applied mostly to the design and administration of pharmaceuticals. We propose that the same paradigm should be applied to biomaterial design and administration. Materials can no longer be considered as ‘one size fits all’ for a broadly defined indication, but should take into account the unique tissue microenvironment of each patient. Little attention has been paid to the role of diseased tissue on material performance, biocompatibility, and healing capacity.
We used a prototypical adhesive material based on dendrimer/dextran to study material-tissue interactions using the colon as a model tissue platform. We studied inflammatory colitis and colon cancer and found not only a difference in adhesion related to surface chemical interactions but also the existence of a complex interplay that determined the overall dendrimer/dextran biomaterial compatibility. Compatibility was contextual, not simply a constitutive property of the material, and was related to the extent and nature of immune cells in the diseased environment present before material implantation. This in turn guided us to an optimal dendrimer/dextran formulation choice using a predictive model based on clinically relevant conditions.
Theranostic materials that provide diagnostics and drug therapy can be exploited to design disease-responsive materials that perform in a patient-specific manner. We took this approach in the design of bioresponsive hydrogel embedded with dark-gold nanoparticles that is able to knockdown specific genes and release a chemotherapeutic drug to combat breast cancer. Gold nanoparticles were modified with drug-intercalated nanobeacons (hairpin DNA) that serve as an ON/OFF molecular nanoswitch triggered by the increased multidrug resistance protein (MRP1) expression within the tumor tissue microenvironment. This nanoswitch can sense and overcome multidrug resistance (MDR) prior to local drug release. The device is designed to report on binding to the target and on drug release via two-color fluorescence emission. We found that MRP1 silencing abolished the tumor despite the cross-resistance to the drug and can be utilized to reverse cross-resistance to many chemotherapeutic drugs. As a universal nanotheranostics probe, this platform can pave the way to early cancer detection and treatment.
Advances in material design and characterization techniques now allow for substantially more sophisticated tuning of biomaterial properties than previously imagined. Versatile biomaterial design can be achieved by addition of tunable building blocks for sensing, repairing, treating, targeting and strengthening. Personalized materials will reduce product failures in (pre)clinical testing and usher in a new chapter in precision medicine.