To reduce the side effects of chemotherapy and reach effective and safe therapy of prostate cancer, herein, a simple but multifunctional system TiO2:Gd@DOX/FA motivated by ultrasound was developed for MRI guided multi-mechanism therapy of prostate cancer. TiO2 nanoparticles served as a sonosensitizer as well as a nanocarrier with pH-responsive release of DOX. Doping of Gd could not only endow TiO2 the ability of magnetic resonance imaging (MRI), but also further improve sonodynamic ability of TiO2. The characterization revealed the as-prepared TiO2:Gd@DOX/FA showed sensitive pH-responsive drug release, high ROS production, T1-MRI contrast performance and excellent biocompatibility. The cytotoxicity assay in vitro showed TiO2:Gd@DOX+Ultrasound group induced cell death up to 91.68% after 48 h incubation. Meanwhile, in vivo synergistic therapy studies, the tumor sizes of all the nanomedicine groups were smaller than free DOX (V:V0=4.2). More importantly, the body nearly showed no weight loss. This safety was also confirmed by the H&E staining, biodistribution experiment and serum biochemistry results. Altogether, TiO2:Gd@DOX/FA significantly reduced the side effect of DOX, augmented the levels of ROS and achieved effective and safe therapy, indicating its potential for multi-mechanism therapy of prostate cancer.
Nanotechnology. 2018 Jan 19 [Epub ahead of print]
Pu Yuan, Dongkui Song
Urinary Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jianshe Road, Zhengzhou, Zhengzhou, Henan, HEN 371, CHINA.