Cong Chen, Feng Jia, Zhibo Hou, Shu Ruan, Qibin Lu

Paeonol (Pae; 2'-hydroxy-4'-methoxyacetophenone) has attracted intense attention as a potential therapeutic agent against various cancers. However, the use of Pae is limited owing to its hydrophobicity. Recently, biodegradable polymeric nanoparticles with amphiphilic copolymers have been used as drug carriers; these have better bioavailability and are promising tumor-targeted drug delivery systems. In the current study, we prepared Pae-loaded nanoparticles (Pae-NPs) with amphiphilic block copolymers using nanoprecipitation. The physiochemical characteristics and antitumor effects of nanoparticles were evaluated in different cancer cells. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed substantial inhibition of cell growth by Pae-NPs. Moreover, lower doses of Pae-NPs inhibited cell growth more efficiently than the equivalent doses of free Pae. Inhibition was characterized by significant elevation of intracellular reactive oxygen species and subsequent inhibition of Akt and regulation of apoptotic proteins, which could be partly reversed by pretreatment with the antioxidant N-acetylcysteine. In vivo results also demonstrated that Pae-NPs could exert much stronger antitumor effects than free Pae. Therefore, Pae-NPs represent a promising delivery system to overcome the low solubility of Pae and enable its use in treating cancer.