2022-2023 Institute for Bioengineering and Bioscience Distinguished Lecture

"Designer Nanocarriers for Cancer Therapy"

Paula T. Hammond, Ph.D.
Institute Professor and Department Head of Chemical Engineering
Koch Institute of Integrative Cancer Research
Massachusetts Institute of Technology

ABSTRACT
One of the challenges of nanomedicine is determining sets of design rules that dictate where nanoparticles localize in the body, and the targeting of specific organs or cell types.  Electrostatic assembly provides a route to nanomaterials that enable a broad range of surface chemistries that can be designed for targeting disease, while incorporating a range of core nanoparticle systems whose properties can be independently tuned.  We have developed a modular nanoparticle approach using core particles and layering them with an electrostatic layer-by-layer (LBL) process in a simple and elegant method of constructing highly tailored ultrathin polymer coatings. The resulting LbL nanoparticles (LbL NPs) have negatively charged outer layers that present polyelectrolytes such as dextran sulfate or hyaluronic acid in a hydrated brush arrangement that enables hydration, steric repulsion, colloidal and serum stability, and specific or non-specific targeting. Ultimately, it is also important to introduce other kinds of interactions, particularly when targeting specific cells such as immune or cancer cells; often these interactions include receptor-specific interactions, but non-specific interactions can also have a very significant role in directing particles to cancer or other disease-associated cell types. Ultimately, we seek to explore and exploit these interactions to target layer-by-layer and layered complex nanoparticles to a range of different cell types. Efforts on the use of high throughput sampling of nanoparticle-cell interactions on understanding nanoparticle-cell interactions and targeted uptake will also be discussed. Recent work includes addressing barriers to transport of these nanoparticles within tumors, and will be discussed, including work involving the understanding of these trafficking patterns and a means to leverage them toward the delivery of cytokines for activation of the immune system against ovarian cancer, a cancer which has not previously benefitted from immunotherapeutic approaches.   Ongoing work also includes examination of the role of mechanical properties of the core nanoparticle in tumor targeting, and how these LbL NP systems might be adapted to enhance delivery across the blood-brain barrier and designed to target glioblastoma. 

BIO
Paula T. Hammond is Institute Professor at the Massachusetts Institute of Technology and the Head of the Department of Chemical Engineering. 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. 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 nanomedicine 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 has developed self-assembled materials systems for electrochemical energy devices.

Professor Paula Hammond was elected into the National Academy of Science in 2019, the National Academy of Engineering in 2017, the National Academy of Medicine in 2016, and American Academy of Arts and Sciences in 2013. She is one of only 25 distinguished scientists elected to all three national academies. She won the ACS Award in Applied Polymer Science in 2018, and 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 2014 AIChE Alpha Chi Sigma Award for Chemical Engineering Research. 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. By developing degradable electrostatically assembled layer-by-layer (LbL) thin films that enable temporal and even sequential controlled release from surfaces, Paula Hammond pioneered a new and rapidly growing area of multicomponent surface delivery of therapeutics that impacts biomedical implants, tissue engineering and nanomedicine. A key contribution is her ability to introduce not only controlled release of sensitive biologics, but her recent advances in actually staging the release of these drugs to attain synergistically timed combination therapies. She has designed multilayered nanoparticles to deliver a synergistic combination of siRNA or inhibitors with chemotherapy drugs in a staged manner to tumors, leading to significant decreases in tumor growth and a great lowering of toxicity. The newest developments from her lab offer a promising approach to messenger RNA (mRNA) delivery, in which she creates pre-complexes of mRNA with its capping protein and synthesized optimized cationic polypeptides structures for the co-complexation and stabilization of the nucleic acid-protein system to gain up to 80-fold increases in mRNA translation efficiency, opening potential for vaccines and immunotherapies. Professor Hammond has published over 320 papers, and over 20 patent applications. She is the co-founder and member of the Scientific Advisory Board of LayerBio, Inc. and a member of the Scientific Advisory Board of Moderna Therapeutics.

IBB welcomes all in Georgia Tech's bio-community to attend, with lunch immediately following the lecture.