Reactive Oxygen Species-Manipulated Drug Release from a Smart Envelope-Type Mesoporous Titanium Nanovehicle for Tumor Sonodynamic-Chemotherapy

【作者】 Jinjin Shi; Zhaoyang Chen; Binghua Wang; Lei Wang; Tingting Lu; Zhenzhong Zhang

【期刊名】 ACS Applied Materials & Interfaces

【影响因子】 2015年:7.221

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2015, 7: 28554-28565

【关键词】 mesoporous titanium dioxide nanoparticle; ROS-manipulated drug release; sonodynamic therapy; combination therapy; nanomedicine

【摘要】Despite advances in drug delivery systems (DDSs), the stimuli-responsive controlled release DDSs with high spatial/temporal resolution are still the best choice. Herein, a novel type of envelope-type mesoporous titanium dioxide nanoparticle (MTN) was developed for one-demand drug delivery platform. Docetaxel (DTX) was loaded in the pores of MTN with a high drug loading efficiency (∼26%). Then β-cyclodextrin (β-CD, a bulky gatekeeper) was attached to the outer surface of MTN via a reactive oxygen species (ROS) sensitive linker to block the pores (MTN@DTX-CD). MTN@DTX-CD could entrap the DTX in the pores and allow the rapid release until a focused ultrasound (US) emerged. A large number of ROS were generated by MTN under US radiation, leading to the cleavage of the ROS-sensitive linker; thus, DTX could be released rapidly since the gatekeepers (β-CD) were detached. Besides, the generation of ROS could also be used for tumor-specific sonodynamic therapy (SDT). Studies have shown the feasibility of MTN@DTX-CD for US-triggered DTX release and sonodynamic-chemotherapy. In the in vitro and in vivo studies, by integrating SDT and chemotherapy into one system, MTN@DTX-CD showed excellent antitumor efficacy. More importantly, this novel DDS significantly decreased the side effects of DTX by avoiding the spleen and hematologic toxicity to tumor-bearing mice.

【全文链接】http://www.ncbi.nlm.nih.gov/pubmed/26587885