International Journal of Nanomedicine (Sep 2017)
Delivery of paeonol by nanoparticles enhances its in vitro and in vivo antitumor effects
Abstract
Cong Chen,1,* Feng Jia,2,* Zhibo Hou,3 Shu Ruan,4 Qibin Lu1 1Department of Gynecology of Traditional Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 2Department of Neurosurgery, Yancheng City No 1 People’s Hospital, The Fourth Affiliated Hospital of Nantong Medical College, Yancheng, 3First Department of Respiratory Medicine, Nanjing Chest Hospital, Medical School of Southeast University, Nanjing, 4Department of Endocrinology, Yancheng Third Hospital, The Affiliated Hospital of Southeast University Medical College, Yancheng, Jiangsu, China *These authors contributed equally to this work Abstract: 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. Keywords: nanoparticles, drug delivery, paeonol
