This NSF CAREER award, funded by the Biomaterials program in the Division of Materials Research to Tuft University, will study an effective approach to deliver proteins intracellularly using a combination of lipid-based nanoparticles and the chemical modification of proteins, for possible biomedical applications. Many protein-based drugs in the market elicit their functionalities by targeting specific cell surface receptors. There are a number of diseases, including genetic diseases and cancers, which have the potential to be treated through proteins with a target inside the cell. However, proteins are usually not able to cross the cell membrane. Hence it is necessary to develop an effective approach to transport the protein inside the cell safely and efficiently. This proposal aims to develop lipid-based nanoparticles to deliver the protein inside the cells. The protein will be chemically modified to facilitate its binding with the lipid nanoparticle. Such a nanocomplex could be efficiently taken up by the cells and the protein will then be released inside the cell to reach the therapeutic targets. This enabling technology may open the door for generating new therapies for a variety of diseases. These results are anticipated to have a positive impact on the fields of nanomedicine and protein based biotherapeutics. The research will advance our understanding of the influence of chemical modification of protein on their physical properties and biological functions. The proposed work will train high school, undergraduate, and graduate students in the area of nanomedicine, and the outreach program will provide an encouraging and collaborative learning program.
There are many protein-based drugs currently available, such as cytokines, growth factors, and monoclonal antibodies. Most of these drugs function by interacting or binding with specific cell surface receptors. However, the delivery of proteins safely and efficiently to intracellular targets remains challenging. An enabling technique that can facilitate the efficient intracellular transduction of proteins or peptides will open the door for generating new therapies for a variety of diseases, including some diseases traditionally viewed as not treatable with drugs. This research will establish a novel method for the reversible modification of proteins, and provide an effective lipid-based nanoparticle formulation that could deliver proteins intracellularly. Such a strategy for intracellular protein delivery could be made universal by easily adapting this delivery method with other proteins or peptides for the development of new drugs for different diseases. This research is expected to advance our understanding of the influence of chemical modification of proteins, on their physical properties, and biological functions. The proposed work will train high school, undergraduate, and graduate students in conducting scientific research in the area of nanobiotechnology. The summer camp program will let the students gain the knowledge and experience of nanobiotechnology, and stimulate the prospective students' passion and interest in sciences at the early stages of their career development.
