A positive feedback strategy for enhanced chemotherapy based on ROS-triggered self-accelerating drug release nanosystem.
Here, a positive feedback strategy was utilized to amplify the concentration of intracellular reactive oxygen species (ROS) and a ROS-triggered self-accelerating drug release nanosystem (defined as T/D@RSMSNs) was demonstrated for enhanced tumor chemotherapy. The mesoporous silica nanoparticles (MSNs) based nanocarriers were gated by β-cyclodextrin (β-CD) through the ROS-cleavable thioketal (TK) linker to encapsulate the anticancer drug doxorubicin hydrochloride (DOX) and ROS producing agent α-tocopheryl succinate (α-TOS), whose surface was further anchored with adamantane conjugated poly(ethylene glycol) chain (AD-PEG) via host-guest interaction. It was found that in human breast cancer (MCF-7) cells, T/D@RSMSNs could not only release DOX and α-TOS initiatively, but also lead to increased concentration of intracellular ROS, which could be used as new trigger to cut away TK linkage and then in turn facilitate the further release of DOX for enhanced chemotherapy. Both in vitro and in vivo experiments demonstrated that T/D@RSMSNs exhibited more significant antitumor activity in the human breast cancer than the traditional single-DOX loaded ROS-responsive nanocarrier. This novel ROS-triggered self-accelerating drug release nanosystem with remarkably improved therapeutic effects could provide a general strategy to branch out the applications of existing ROS-responsive drug delivery systems (DDSs).
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Jing-Jing
JJ
Hu
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Qi
Q
Lei
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Meng-Yun
MY
Peng
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Di-Wei
DW
Zheng
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Yi-Xuan
YX
Chen
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China. Electronic address: xz-zhang@whu.edu.cn.
Xian-Zheng
XZ
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D065546:Drug Liberation; D025461:Feedback, Physiological; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D016062:Porosity; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012822:Silicon Dioxide / Q000737:chemistry; D024502:alpha-Tocopherol / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D024502:alpha-Tocopherol
Drug delivery; Mesoporous silica nanoparticle; Positive feedback strategy; ROS-responsive; Tumor therapy