nanoparticles for intracellular drug and vaccine delivery
We are developing nanoparticles designed for diverse applications in vaccines, immunotherapy, and generalized drug delivery. Of particular interest are nanoparticles that can deliver protein or peptide antigens in concert with immunostimulatory ligands to dendritic cells, for subsequent priming of T- and B-lymphocytes. We are also studying the properties of small nanoparticles (< 10 nm in diameter) bearing amphiphilic charged and hydrophobic surface functionalities; these nanomaterials have the capacity to strongly interact with membranes of living cells, and depending on composition and size, can embed within or pass through lipid bilayers without permanent disruption of the membrane. These novel nanomaterials may provide a new way to achieve for highly efficient delivery of drugs or diagnostic agents into cells for therapy or monitoring of cellular processes.
(Left) pH-responsive gel particles (red) being internalized by dendritic cells (green), key immune sentinels that regulate the initiation of immune responses. (Right) Cartoon representation of “striped” gold nanoparticles, each ~10 nm in diameter and coated with an organized rippled nanostructure presenting hydrophilic sulfonate and hydrophobic methyl groups. These particles are capable of penetrating the external membrane of cells, entering the cytosol without toxicity or disruption of the integrity of the plasma membrane. These particles may provide a new way to efficiently deliver drugs or diagnostic agents into cells.
pH-responsive gel particles (blue) disrupt endolysosomes (purple) in dendritic cells, allowing a small molecule (calcein, green) to flood throughout the cytosol of these cells. These particles may be useful as delivery agents for vaccines, RNA interference-based therapeutics, or gene therapy.
