Gambogic acid-loaded PEG–PCL nanoparticles act as an effective antitumor agent against gastric cancer.

Poor water solubility and side effects hampered the clinical application of gambogic acid (GA) in cancer therapy. Accordingly, GA-loaded polyethylene glycol-poly(ɛ-caprolactone) (PEG–PCL) nanoparticles (GA-NPs) were developed and administered peritumorally to evaluate their antitumor activity. The particle size, polydispersity index, encapsulation efficiency and loading capacity of GA-NPs were 143.78 ± 0.054 nm, 0.179 ± 0.004, 81.3 ± 2.5% and 14.8 ± 0.6%, respectively. In addition, GA-NPs showed excellent stability, good biocompatibility and sustained release profile. Endocytosis studiesin vitrodemonstrated that the GA-NPs were effectively taken up by tumor cells in a time-dependent manner.In vivoreal-time imaging showed that the nanoparticles effectively accumulated within the tumor tissue after peritumoral administration. The cytotoxicity study revealed that the GA-NPs effectively inhibited the proliferation of gastric cancer cells. In vivoantitumor therapy with peritumoral injection of GA-NPs exhibited superior antitumor activity compared with free GA. Moreover, no toxicity was detected in any treatment group. Histological studies confirmed a lower cell density and a higher number of apoptotic cells in the GA-NPs group compared with the free GA group. Furthermore, the expression level of the cysteine proteases 3 precursor (pro-caspase3), a crucial component of cellular apoptotic pathways, was efficiently reduced in mice treated with GA-NPs. In conclusion, the GA-NPs system provided an efficient drug delivery platform for chemotherapy. [ABSTRACT FROM PUBLISHER]