David H. Koch (1962) Professor of Engineering
Head of the Department of Chemical Engineering
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"Our laboratory emphasizes the molecular design and synthesis of self-assembling polymeric systems for a range of biological applications. In cancer research, we focus on the generation of polymer-based films and nanoparticles for drug delivery. Nanoparticles have the potential to protect drugs in the blood stream during delivery so that they are not prematurely broken down or excreted. They increase solubility, accessibility, and longevity so that a potent drug can more easily reach the tumor. We have developed ways to create combination nanoparticles that contain siRNA, which can silence or block a gene that enables tumors to be resistant to drugs, and a chemotherapy agent. We have also been designing nanoparticles with outer surfaces that bind specifically to different kinds of cells, including tumor and immune cells, to create improved immunotherapies against cancer. We are especially interested in using these tools to address challenging cancers, including ovarian cancer and glioblastoma."
Professor Paula T. Hammond is the David H. Koch (1962) Professor of Engineering at the Massachusetts Institute of Technology, and the Head of the Department of Chemical Engineering. Professor Hammond is a member of the National Academy of Sciences, the National Academy of Engineering, and the National Academy of Medicine, as well as the American Academy of Arts and Sciences. She is a member of MIT’s Koch Institute for Integrative Cancer Research 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. Prof. Hammond’s has also worked on the development of new biomaterials using directed and self-assembly of polymers, including drug delivery systems containing biologic protein and nucleic acid based therapeutics, and coatings to promote tissue regeneration. Areas of application have included targeted cancer nanomedicine, vaccines, drug releasing biomedical implants, and growth factor and siRNA release for wound healing and bone regeneration. In the area of cancer, she investigates novel responsive polymer architectures for targeted nanoparticle drug and gene delivery, and the generation of cancer vaccines and delivery of agents to activate the immune response in the tumor microenvironment.
Dr. Hammond is a Board Member and co-Founder of LayerBio, Inc., a member of the Scientific Advisory Board of Moderna Therapeutics, Inc., the Scientific Advisory Board of Camden Partners LLC, and a member of the Board of Alector, Inc.
Professor Hammond is a recipient of many awards, among them the American Institute of Chemical Engineers (AIChE) Margaret H. Rousseau Pioneer Award for Lifetime Achievement by a Woman Chemical Engineer, 2019; Materials Research Society (MRS) David Turnbull Lectureship, 2019; ETH Zurich Chemical Engineering Medal, 2019; American Chemical Society Award in Applied Polymer Science, 2018.
Prof. Hammond's research interests include:
In our research group, we use the principles of electrostatic assembly in polymers, and directed self-assembly to create drug delivery systems that can provide unique modes of release in which drugs are co-delivered or delivered in sequence to targeted cells, and by which tumor cells are targeted using multiple modes. We have continued to use this approach to develop nanoparticles capable of delivering combination therapies for ovarian cancer, as well as difficult to treat breast, lung and brain cancers.
The Layer-by-Layer (LbL) nanoparticle is a promising drug delivery platform with great clinical translational potential. Utilizing the process of depositing oppositely charged polyelectrolytes sequentially on a charged core, LbL nanoparticles possess hierarchical and multifunctional multilayered structure with great modularity and versatility. LbL nanoparticles have several desirable features, including precise control of size, combinatory therapeutics with high loading capacity, staged cargo release, enhanced stability in vivo, and tunable surfaces for modification. It is possible to incorporate therapeutics such as RNA, small molecule inhibitor drugs, or proteins in nanolayers wrapped around a charged colloidal core that contains a chemotherapy drug capable of killing cancer cells, such as doxorubicin or cisplatin. Furthermore, the LbL platform can introduce different polymeric surface chemistries that enable targeting of the slightly acidic tumor tissues, and the presence of specific ligands that attach to a number of known aggressive tumor cell types, from ovarian to lung cancer, via the binding to a receptor that is highly expressed on the surfaces of these cancer cells.
What is particularly exciting about these nanolayered particle systems is that we can layer negatively charged nucleic acids – including silencing RNAi and microRNA’s that either silence or replace specific genes that cause tumorigenic behavior – into these LbL coatings. These multi-drug loaded nanoparticles make it possible to combine targeted RNAi-based therapeutics to improve the anticancer effects of frontline chemotherapy drug. We have adapted these nanoparticles for theranostic applications in our collaborations, and manipulated them to enable targeting across the blood-brain barrier for glioblastoma. Additional work includes novel ways to deliver mRNA using protein-RNA complexes, and the delivery of cytokines, immunogens and/or adjuvants for immunotherapy applications.
K.Y. Choi, S. Correa, J. Min, J. Li, S. Roy, K.H. Laccetti, E.C. Dreaden, S. Kong, H. Roun, Y.H. Roh, E.C. Lawson, P.A. Palmer, P.T. Hammond, “Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo using Layer-by-Layer Nanoparticles”, Advanced Functional Materials, 29, 20, (2019).
C. Wu, J. Li, W. Wang, P.T. Hammond, “Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated Gene Silencing”, ACS Nano 12, 6504–6514 (2018).
F.C. Lam, S.W. Morton, J. Wyckoff, T.-L. Vu Han, M. K. Hwang, A. Maffa, E. Balkanska-Sinclair, M.B. Yaffe, S.R. Floyd, and P.T. Hammond, “Enhanced In Vivo Efficacy and Safety of Combination Temozolomide and Bromodomain Inhibitor Therapy for Gliomas Using a Targeted Dual Drug-loading Stealth Liposomal Carrier”, Nature Comm., 9, article no. 1991, doi:10.1038/s41467-018-04315-4, (2018), PMCID: PMC5959860
E.C. Dreaden, Y.W. Kong, M.A. Quadir, S. Correa, L. Suárez-López, A.E. Barberio, M.K. Hwang, A.C. Shi, B.Oberlton, P.N. Gallagher, K.E. Shopsowitz, K.M. Elias, M.B. Yaffe, and P. T. Hammond, “RNA-Peptide Nanoplexes Drug DNA Damage Pathways in High-Grade Serous Ovarian Tumors”, Bioengineering & Translational Medicine, 3, 26-36, (2018), PMCID:PMC5773954
L. Gu, J.Z. Deng, S. Roy, P. T. Hammond, “A Combination RNAi-Chemotherapy Layer-by-Layer Nanoparticle for Systemic Targeting of KRAS/P53 with Cisplatin to Treat Non-small Cell Lung Cancer”, Clin. Cancer Res., 23, 7312-7323 (2017), PMCID: PMC5712246
J. Li, W. Wang, Y. He, Y. Li, E.Z. Yan, K. Zhang, D.J. Irvine, P.T. Hammond, “Structurally Programmed Assembly of Translation Initiation Nanoplex for Superior mRNA Delivery, ACS Nano, 11, 2531-2544 (2017), PMCID: PMC5629916
S. Correa, K.Y. Choi, E. C. Dreaden, K. Renggli, A. Shi, L.Gu, K. E. Shopsowitz, M.A. Quadir, E. Ben-Akiva, P.T. Hammond, "Highly scalable, closed-loop synthesis of drug-loaded, layer-by-layer nanoparticles", Advanced Functional Materials, 26, 991-1003, (2016), PMCID: PMC4847955
E.C. Dreaden, Y.W. Kong, S.W. Morton, S. Correa, K.Y. Choi, K.E. Shopsowitz, K. Renggli, R. Drapkin, M.B. Yaffe, P.T. Hammond, “Tumor-Targeted Synergistic Blockade of MAPK and PI3K from a Layer-by-Layer Nanoparticle”, Clin. Cancer Res., 21, 4410-9, (2015), PMCID: PMC4624301
S.W. Morton, N.J. Shah, M.A. Quadir, Z.J. Deng, Z. Poon, P.T. Hammond, “Osteotropic Therapy via Targeted Layer-by-Layer Nanoparticles”, Advanced Healthcare Materials, 3, 867-875 (2014), PMCID: PMC4041853
Z.J. Deng, S.W. Morton, E. Ben-Akiva, E.C. Dreaden, K.E. Shopsowitz, P.T. Hammond, “Layer-by-Layer Nanoparticles for Systemic Codelivery of an Anticancer Drug and siRNA for Potential Triple-Negative Breast Cancer Treatment”, ACS Nano, 7, 9571-84 (2013), PMCID: PMC3870477