Herein, we aimed to prepare receptor-selective HA-coated PLGA nanoparticles (HA-PLGA-API-NPs) for colon cancers with high expression of CD44; chitosan (CS) was introduced into the system as an intermediate, simultaneously binding HA and PLGA through electrostatic interaction to facilitate a tighter connection between them. Here, CD44 is linked to colonic neoplasm.