5-Aminolevulinic acid (ALA) is a FDA-approved photodynamic therapy (PDT) precursor of protoporphyrin IX (PpIX) used for treating various cancers. However, the internalization of ALA is a big challenge due to its hydrophilic nature and low specificity to cancer cells. In this work, ALA conjugated prodrug nanoparticles were prepared by conjugation of thiolated stealth peptide sequence CPPPPEKEKEKEKEKEDGR and hydrazone-containing ALA to gold nanoparticles (AuNPs). Remarkable anti-fouling ability of ALA prodrug nanoparticles in complex environment was achieved owing to the zwitterionic stealth peptide sequence EKEKEKEKEK. The release of ALA could be greatly accelerated upon incubation of ALA prodrug nanoparticles in lysosomal/endosomal pH (pH 5.5). Meanwhile, the cellular internalization could be greatly enhanced by RGD moieties. MTT results demonstrated that ALA prodrug nanoparticles exhibited better photodynamic cytotoxicity than free ALA after light irradiation, suggesting enhanced photodynamic therapeutic efficacy. (C) 2016 Elsevier Inc. All rights reserved.