title: Reactive Oxygen Species-Manipulated Drug Release from a Smart Envelope-Type Mesoporous Titanium Nanovehicle for Tumor Sonodynamic-Chemotherapy.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.|Collaborative Innovation Center of New Drug Research, Safety Evaluation, Henan Province, Zhengzhou 450001, P.R. China.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.
authors.forename: Binghua
authors.initials: B
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , Zhengzhou 450001, P.R. China.|Collaborative Innovation Center of New Drug Research, Safety Evaluation, Henan Province, Zhengzhou 450001, P.R. China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D043823:Taxoids / Q000008:administration & dosage / Q000737:chemistry; D014025:Titanium / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D017382:Reactive Oxygen Species; D043823:Taxoids; C009495:titanium dioxide; D000077143:Docetaxel; D014025:Titanium
keywords: ROS-manipulated drug release; combination therapy; mesoporous titanium dioxide nanoparticle; nanomedicine; sonodynamic therapy