TRB Distinguished Biomaterials Lecture

Paula Hammond, PhD: Electrostatic Designer Nanocarriers for Targeted Therapies

The 2023 Distinguished Biomaterials Lecture was held in conjunction with the TRB-QBP-SB2 Symposium.

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 tailed 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 benefited from immuniotherapeutic 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.

Professor Paula T. Hammond is an Institute Professor at the Massachusetts Institute of Technology, Head of the Department of Chemical Engineering and a member of MIT’s Koch Institute for Integrative Cancer Research. Her research in nanomedicine encompasses the development of new biomaterials to enable drug delivery from surfaces with spatio-temporal control. She investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery, and is known for her work on nanoparticles to target cancer, and thin film coatings to release factors that regenerate bone and assist in wound healing. More recently, she has worked on nanomaterials systems to treat osteoarthritis and staged release systems for the delivery of vaccines. 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 the 2013 Class of the American Academy of Arts and Sciences. She has also recently received the American Institute of Chemical Engineers (AIChE) Margaret H. Rousseau Pioneer Award for Lifetime Achievement by a Woman Chemical Engineer in 2019 and gave the Materials Research Society (MRS) David Turnbull Lectureship, 2019. Professor Hammond has published over 330 papers, and over 20 patent applications. She is the co-founder and member of the Scientific Advisory Board of LayerBio, Inc., a member of the Scientific Advisory Board of Moderna Therapeutics and a member of the Board of Alector, Inc. In 2021, Professor Hammond was selected to become a member of the President’s Council of Advisors on Science and Technology (PCAST). In terms of educational background, Prof. Hammond is from Detroit, Michigan, and received her B.S. in Chemical Engineering from MIT, then worked for two years in industry, moved to Atlanta to get an M.S. in Chemical Engineering at Georgia Tech, before returning to MIT for her PhD. She held the Ford Foundation Dissertation Fellowship, and on completing her PhD, was an NSF Postdoctoral Fellow at the Harvard University Chemistry Department before returning to MIT as a faculty member.

 

Past TRB Distinguished Biomaterials Lectures