Co-encapsulation of magnetic Fe3O4 nanoparticles and doxorubicin into biodegradable PLGA nanocarriers for intratumoral drug delivery

Abstract

Yanhui Jia1, Mei Yuan1, Huidong Yuan1, Xinglu Huang2, Xiang Sui1, Xuemei Cui1, Fangqiong Tang2, Jiang Peng1, Jiying Chen1, Shibi Lu1, Wenjing Xu1, Li Zhang1, Quanyi Guo11Institute of Orthopedics, General Hospital of the Chinese People's Liberation Army, Beijing, People's Republic of China; 2Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, People's Republic of ChinaAbstract: In this study, the authors constructed a novel PLGA [poly(D,L-lactic-co-glycolic acid)]-based polymeric nanocarrier co-encapsulated with doxorubicin (DOX) and magnetic Fe3O4 nanoparticles (MNPs) using a single emulsion evaporation method. The DOX-MNPs showed high entrapment efficiency, and they supported a sustained and steady release of DOX. Moreover, the drug release was pH sensitive, with a faster release rate in an acidic environment than in a neutral environment. In vitro, the DOX-MNPs were easily internalized into murine Lewis lung carcinoma cells and they induced apoptosis. In vivo, the DOX-MNPs showed higher antitumor activity than free DOX solution. Furthermore, the antitumor activity of the DOX-MNPs was higher with than without an external magnetic field; they were also associated with smaller tumor volume and a lower metastases incidence rate. This work may provide a new modality for developing an effective drug delivery system.Keywords: antitumor activity, external magnetic field, intratumoral injection, apoptosis, Lewis lung carcinoma