Intracellular Delivery of Biomolecules Using Nanomaterials
Gustin Laboratory
Many infectious agents, including viruses and some bacteria, fungi, and parasites, enter and persist in host cells, allowing them to evade immune mechanisms and antibiotics. In addition, it is common for some pathogens to target specific organelles once inside the cell. The ability to deliver molecules intracellularly will allow us to directly prevent and/or disrupt cellular activities required for replication of these normally persistent human and animal pathogens. In addition, the development of this technology, concomitant with efficient cell targeting could have applications in cancer therapy by providing an alternative to the use of immunotoxins for combating tumors. Importantly, this work can also be extended to the study of basic cell biological processes through the delivery of markers or reagents to specific subcellular compartments.
Work over the past two years has resulted in the successful exploitation of integrins, host cell surface receptors that bind to fibronectin, an extracellular matrix protein. Many bacteria take advantage of fibronectin’s ability to interact with integrins by expressing fibronectin binding proteins that target them to the cell surface and facilitate internalization. In collaboration with Dr. McIlroy in the Physics Department we found that coating nanowires with fibronectin enabled internalization of the nanowires into human and bovine epithelial cells in vitro (Beaux et al., 2006, J. Biomed. Nanotech,, 2:23-28). These findings present a method for the delivery of biologically active compounds directly into cells. The proposed project will further our understanding of this delivery system and develop its use for therapeutics and basic research applications through three specific aims:
Aim 1: Maximize protein coating and internalization efficiency of nanowire-protein complexes.
Aim 2: Delivery of biologically active agents to the intracellular environment.
Aim 3: Targeting nanowire-protein complexes to subcellular organelles.
