The Caged Drugs Sing: Killing Cancer with Nano
February 11, 2015
Paula T. Hammond
David H. Koch Professor of Chemical Engineering, M.I.T.
The design of nanoparticles for the delivery of drugs to tumors and other specific regions of the body requires versatile chemistry and the ability to manipulate nanoparticle surfaces with the high level of control needed multiple kinds of targeting. The means by which such nanostructured particle systems can be achieved using two different approaches - block copolymers and polyelectrolyte layer-by-layer assembly (LbL) methods - will be addressed. We have used responsive synthetic polypeptide copolymers as a means of generating unique polymersome and micellar carriers. These polymers include clickable polypeptide block copolymers substituted with various amine moieties that range in pKa and hydrophobicity and designed to destabilize in the endosome. These systems can be further functionalized to target specific cells using ligand-cluster arrangement on particle surfaces, and make unique nanoscale drug carriers for systemic delivery in applications such as targeted cancer chemotherapy. On the other hand, it is possible to design nanoparticles that consist of several nanolayers wrapped around a core materials system using LbL nanoparticles. These polyelectrolyte nanolayer assemblies can be generated to increase the half-life of the particle in the bloodstream by preventing adsorption of proteins via hydrated outer layers, and acting as a “stealth” layer that prevents recognition of the particle as a foreign body by the body’s defense systems, and yet facilitate cell entry in the hypoxic tumor microenvironment and molecular targeting for specific tumor targets. We show the synergistic combination release of siRNA and chemotherapeutics in a time-dependent or staggered fashion that enables synergistic cancer cell killing effects both in vitro and in vivo. Finally, newer synthetic methods in our laboratory that include the use of rolling circle transcription to create concatenated-siRNA that can be assembled into nanostructures, and the resulting assembled systems will be discussed.
About the Speaker
Professor Paula T. Hammond is the David H. Koch Chair Professor of Engineering in the Chemical Engineering Department at the Massachusetts Institute of Technology. She is a member of MIT’s Koch Institute for Integrative Cancer Research, the MIT Energy Initiative, and a founding member of the MIT Institute for Soldier Nanotechnology. She recently served as the Executive Officer (Associate Chair) of the Chemical Engineering Department (2008-2011). The core of her work is the use of electrostatics and other complementary interactions to generate functional materials with highly controlled architecture. Her research in nanotechnology encompasses the development of new biomaterials to enable drug delivery from surfaces with spatio-temporal control. She also investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery, and self-assembled materials systems for electrochemical energy devices.
Professor Paula Hammond was elected into the 2013 Class of the American Academy of Arts and Sciences. She is also the recipient of the 2013 AIChE Charles M. A. Stine Award, which is bestowed annually to a leading researcher in recognition of outstanding contributions to the field of materials science and engineering, and the Alpha Chi Sigma Award for Chemical Engineering Success. She was selected to receive the Department of Defense Ovarian Cancer Teal Innovator Award in 2013, which supports a single visionary individual from any field principally outside of ovarian cancer to focus his/her creativity, innovation, and leadership on ovarian cancer research. During her sabbatical in 2013, she was a visiting scientist at the Dana-Farber Cancer Institute, and a visiting professor at the Nanyang Technological University in Singapore, in the Chemical Engineering Department. Prof. Hammond continues to serve as an Associate Editor of the American Chemical Society journal, ACS Nano. As a part of the Year of Chemistry in 2011, she was one of the Top 100 materials scientists named by Thomson-Reuters, a recognition of the highest citation impact in the field over the past decade (2001-2011). She has published over 200 papers, and holds over 20 patents based on her research at MIT. She was named a Fellow of the American Physical Society, the American Institute of Biological and Medical Engineers, and the American Chemical Society Polymer Division. In 2010, she was named the Scientist of the Year by the Harvard Foundation. Other selected honors include the Melvin Calvin Lecturer at UC Berkeley Department of Chemistry, the Margaret Etters Lecturer at the University of Minnesota, and the Caltech Kavli Distinguished Lecturer. Professor Hammond’s work on multilayer tattoos for transdermal DNA vaccines was recently featured on the PBS Nova program, “Making Stuff” with David Pogue, and she was also featured in the Chemical Heritage Foundation’s Catalyst Series: Women in Chemistry.