Polymeric nanoparticle drug delivery systems have tremendous potential for controlled release of therapeutic agents (e.g., small molecules, siRNA) to targeted cells under physiological conditions. However, degradation of commonly used polyester-based delivery systems relies on bulk erosion hydrolysis and is thus very slow and unresponsive to the range of physiological conditions found within cells and tissues. The goal of my research is to synthesize an acid-degradable, acid-amplifying nanoparticle that is sensitive to the lower pH values observed in endosomes and among certain tissues. My initial challenge has been to develop a system that is stable to physiological pH (7.4), but quickly degrades at endosomal pH (6.0-6.5). These features would promote endosomal release as well as enable targeting of acidic cancer tissues. Thus, two potential applications on which I am focused are (1) improved delivery into cells via endocytosis and (2) amplifying the slightly acidic pH in tumor tissue for targeting of cancer cells.