Gastric cancer is the third leading cause of cancer-associated death worldwide. Although a decrease in its incidence is observed, gastric cancer still poses a major clinical challenge due to poor prognosis and limited treatments. Barbaloin (BBL) is a main medicinal composition of the Chinese traditional medicine aloe vera. BBL has various bioactivities, including anti-oxidant, anti-inflammatory and anti-tumor properties. Polydopamine (pD)-based surface modification is easy to functionalize polymeric nanoparticles (NPs) surfaces with ligands and/or additional polymeric layers. In the present study, BBL-loaded formulations was developed with pD-modified NPs, which was synthesized by polylactide-TPGS (PLATPGS) (pD-PLA-TPGS/NPs). And galactosamine (Gal) was conjugated on the prepared NPs (Gal-pD-PLATPGS/NPs) for targeting the gastric cancer cells. Here, we found that BBL-loaded Gal-pD-PLA-TPGS/NPs showed the highest cellular uptake efficacy in gastric cancer cells. Gal-pD-PLA-TPGS/NPs more significantly reduced the gastric cancer cell viability. Further, greater apoptosis, autophagy and ROS generation was induced by Gal-pD-PLA-TPGS/NPs in gastric cancer cells. Additionally, compared to the other two NPs, Gal-pD-PLA-TPGS/NPs most markedly decreased ATP levels in gastric cancer cells. In vivo, Gal-pDPLA-TPGS/NPs were specifically targeted to tumor site. Moreover, Gal-pD-PLA-TPGS/NPs exhibited the most anti-tumor effects, as evidenced by the lowest tumor volume and tumor weight. Of note, there was no significant difference was observed in body and liver weight, as well as the histological changes in major organs isolated from each group of mice. Together, the findings indicated that BBL-loaded Gal-pD-PLA-TPGS/NPs could be targeted to gastric cancer cells to suppress tumor progression without toxicity. (C) 2018 Published by Elsevier Inc.