(617b) Engineering Particle Shape to Enhance Cellular Targeting

Nanoparticulate drug carriers have enormous potential to deliver macromolecular therapeutic agents such as proteins, nucleic acids and antibodies to disease sites. However, the therapeutic efficacy of particulate-based systems largely depends on their adhesion to the cell surface and intracellular uptake. Numerous attempts have been made to improve the cell membrane attachment ability and internalization of particulate-based drugs by optimizing nanoparticle size and surface decoration using ligands such as monoclonal antibodies. However, the effect of nanaoparticle shape on cell-membrane binding, cellular internalization and subsequent therapeutic activation using particulate-based drugs has not received much attention. Here we demonstrate that the specificity and cellular internalization of particulate-based drugs can be dramatically improved by engineering nanoparticle shape. We studied cell-membrane attachment and uptake of monoclonal antibody-modified spherical and rod-shaped nanoparticles in various cell lines. Antibody-coated rod-shaped nanoparticles exhibited high cell-membrane adhesion and intracellular uptake in vitro compared to that using spherical and disk-shaped nanoparticles. Mechanisms of shape-induced enhancement will be discussed. These results highlight the importance of the interplay between nanoparticle shape and antibody interaction with target cells for imaging, diagnostic and therapeutic drug delivery.