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LLE: Electrostatic Assembly for Nanoparticle Targeting of Cells and Tissues
Abstract
Nanomaterials of many types have been applied to address biomedical challenges, particularly in the delivery of drug to targeted regions of the body. One of the most powerful interactions that can regulate tissue transport and nanomaterial trafficking is electrostatic charge. In our lab, we have used electrostatic assembly methods in conjunction with well-defined charged macromolecules to enable delivery of drug to specific tissues or organs based on a combination of multivalent charge interactions coupled with other secondary non-specific or specific binding interactions. These systems vary from highly designed synthetic vectors that can deliver mRNA and even gene editing systems to electrostatically assembled complexes that can be generated with a great deal of control. The generation of such systems requires, in each case, a tuning of the ratio of charged species, and an ability to direct responsive behavior that enables release in such systems.
In one approach, a layer-by-layer (LbL) technique toward construction of nanostructured nanoparticles provides multiple advantages for chemotherapy. We have generated LbL outer layers that provide effective stealth properties, with long systemic plasma blood half lives and higher tumor accumulation over time. We have demonstrated efficacy in genetically induced non-small cell lung cancer mouse models in which key siRNA targets have been selected with chemotherapy drug in the same nanoparticle system, and are now examining new siRNA and drug combinations in ovarian cancer. 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 are exploring ways to utilize these differences in affinity for more selective tumor cell binding and deliver within cells. Ongoing work that includes new ovarian cancer and lymphoma efforts utilizing siRNA and combination drug therapies will be discussed, including new work involving the delivery of cytokines for activation of the immune system against cancer.
Bio
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.
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