Targeting tumors with nanoparticles
The Hammond Lab develops polymeric nanomaterials for cell regeneration and drug release
Since its founding in 1995, the Hammond Lab has been an integral part of the Koch Institute for Integrative Cancer Research, developing nanoparticles that encapsulate and release drugs to reprogram cancer cells. Chemical engineering department head Paula Hammond ’84, Ph.D ’94 leads research initiatives that range from designing thin films for tissue regeneration to embedding nucleic acids into nanomaterials to silence cancer cell expression.
Hammond Lab researchers use a layer-by-layer process to create ultra-thin films that can enclose dissolved biological materials. “You are absorbing positively charged material until the charge is reversed, and then negatively charged material until the charge is reversed. And because it’s a self-limiting process, each layer of material that is absorbed is only a few nanometers thick,” Hammond explained. These films allow researchers to program the transport and release of proteins and nucleic acids in the body. The lab also develops materials that rapidly release peptides for blood clotting and wound healing.
According to Hammond, a central focus of the lab is to “use these layer-by-layer nanoparticles to target tumors selectively over healthy cells, [which] allows us to design combination therapies.” In particular, the lab enhances the effectiveness of chemotherapy drugs by combining them with nucleic acids such as siRNA (which silences genes that enable cancer cell survival) and microRNA (which replaces functions that were lost in healthy cells during the growth of cancer). The layer-by-layer architecture enables the “staged release” of drugs, so that researchers can block different genetic pathways in specific time frames to orchestrate cancer cell death.
Natural biological barriers, such as the blood vessels in the blood-brain barrier, often make the transport of large nanomaterials difficult. To address this problem, Hammond Lab researchers have developed ligands that use transcytosis, a process in which nanoparticles are taken in at one end of a cell and ejected from the other. Another major challenge involves the stability of siRNA. The nanoparticles must be designed so that the siRNA remains stable during its transport in the bloodstream but destabilizes once it enters the tumor cell, where it can interfere with mRNA to prevent the expression of cancer genes.
Hammond recalls several exciting moments in the lab’s 25-year history. In 2006, she collaborated with Professor Angela Belcher, head of the Department of Biological Engineering, to design a layer-by-layer electrochemical battery that contained nanoscale wires made from viruses. This project was published in Science. More recently, the lab has pioneered new methods in combination therapy for tumor targeting: “We’ve been very excited about the fact that we can deliver nucleic acids, including siRNA, directly to wounds. For me, that means that we may be able to deliver other kinds of nucleic acids like gene editing components directly to tissues as well,” Hammond said.
Currently, the lab is developing an immunotherapy for ovarian cancer. In collaboration with biological engineering and materials science professor Darrell Irvine Ph.D ’00, the lab has incorporated cytokines (proteins that activate the immune system) into a new type of nanoparticle that can “sit on the outside of tumor cells rather than go inside them,” Hammond said. She believes this treatment, which has been successfully tested in model mice, could potentially raise the long-stagnant ovarian cancer survival rate.
Hammond also looks forward to applying biological nanoparticles to treat resistant infectious disease. Through the Singapore-MIT Alliance for Research and Technology, researchers have used the Hammond Lab’s technology to encapsulate antibiotics in nanoparticles and disrupt the protective biofilm surrounding pathogenic bacteria. “Here, instead of targeting cancer cells, we’re targeting bacteria cells. Here, instead of the barrier being these epithelial, these blood vessel linings, it’s this biofilm that the bacteria build,” Hammond said.
More broadly, the lab aims to develop nanomaterials that circulate in the bloodstream and target different cell types, taking on immune cell functions. Looking towards the future, Hammond hopes that “if we can do that, we can not only generate disease-targeting nanoparticles more effectively and target a broader set of diseases, but we might be able to design nanoparticles that can monitor the immune state, treat the immune disease or chronic disease, and help us characterize it.”