CBE Julian C. Smith Lecture Series: Paula Hammond, Massachusetts Institue of Technology

Description

Monday, May 3 @ 4:00 PM Programming Medical Treatment One Nanolayer at a Time By alternating positively and negatively charged molecules in sequence, it is possible to generate thin films one nano-layer at a time while controlling the composition of the film with great precision. This electrostatic layer-by-layer (LBL) process is a simple and elegant method of constructing highly tailored ultrathin polymer and organic-inorganic composite thin films. We have used this method to develop thin films that can encapsulate and release proteins and biologic drugs such as growth factors with highly preserved activity from the surfaces of biomedical implants or wound dressings with sustained release over periods of several days. We have engineered coatings that yield release of different drugs, DNA or protein, resulting in highly tunable multi-agent delivery nanolayered release systems for tissue engineering, biomedical devices, and wound healing applications. Depending on the nature of the LbL assembly, we can generate thin films that rapidly release proteins or peptides within minutes for rapid hemostasis to stop bleeding in soldiers on the battlefield, or release growth factors that help to regenerate bone in defects where bone may no longer grow. Finally, the manipulation of charge to target other tissues, in particular cartilage, is an important means of targeting the joint for osteoarthritis. We have generated unimolecular charged systems that can be precisely tuned to achieve deep penetration into avascular tissues such as cartilage to enable extended release treatments for cartilage regeneration. These and other uses of controlled polyelectrolytes and their complexes for delivery within tissues and across barriers will be addressed. Tuesday, May 4 @ 4:00 PM Charged Electrostatically Assembled Nanoparticles for Targeted Delivery We have developed a modular nanoparticle approach using liposomal 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. We have demonstrated that these particles have long systemic plasma blood half-lives and good tumor accumulation over time, and demonstrate efficacy in advanced breast and lung cancer models in which siRNA targets have been delivered with chemotherapy drug in the same nanoparticle system. By staging release of different drug components via the adaptation of the nanoparticle structure, we can achieve highly synergistic release behavior in these systems. We have found that certain LbL nanoparticle formulations traffic differently in cells based on the negatively charged polypeptide, and we are exploring ways to utilize these differences in affinity for more selective tumor cell binding and deliver within cells. Ongoing work includes addressing barriers to transport of these nanoparticles relevant to tumor or other tissue penetration, and will be discussed, including new 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. In vitro and in vivo results will be discussed, as well as release mechanisms, toxicity studies and clinical outlook for these targeted systems. Ongoing work includes examination of how these LbL NP systems might be adapted to enhance delivery across the blood-brain barrier for glioblastoma, or modified to enhance tumor accumulation and penetration. Biography: Professor Paula T. Hammond is the David H. Koch Chair Professor of Engineering 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 also investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery. She 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. 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 AIChE Margaret Rousseau Award. 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. and a member of the Scientific Advisory Board of Moderna Therapeutics.