The gastrointestinal tract has very harsh and varied pH conditions, preventing most oral therapeutic drugs from being effectively delivered to the colon area. On page 714, Ling Xue Kong et al. describe a pH-sensitive drug-delivery system with enhanced drug loading developed by coating 5-fluorouracil (5-FU)-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with Eudragit S100. The 5-FU/PLGA NPs can survive the very acidic gastrointestinal environment and then release 5-FU at pH 7.4, the pH of the colon and rectum. This provides a promising route for the oral treatment of colorectal cancer.