Polymeric nanoparticles for targeted delivery of therapeutic vaccines to dendritic cells

Dendritic cells (DCs) are the sentries of the immune system. They detect pathogens entering the body and activate immune responses against them through multiple nanoscopic molecular interactions. Pathogen-mimicking nanoparticles capable of such interactions were fabricated by incorporating monophosphoryl lipid A in a biodegradable polymer, poly(D,L-lactic-co-glycolic acid) (PLGA). The uptake of PLGA nanoparticles by human and mouse DCs was conclusively demonstrated by confocal laser scanning microscopy. Delivery of antigens in PLGA nanoparticles was shown to be more efficient than their delivery in soluble form for activation of T cell responses against a variety of antigens including a MUCI peptide (BLP25) cancer vaccine. A PLGA nanoparticulate formulation of BLP25 induced potent T cell responses and anticancer effects in a mouse lung cancer model. These results indicate that PLGA nanoparticles mimicking certain features of pathogens are efficient delivery systems for targeting therapeutic vaccines to DCs and activation of potent T cell responses.