Gated magnetic mesoporous silica nanoparticles for intracellular enzyme-triggered drug delivery.
The targeting drug release is significant to the anticancer treatment. In this context, the redox-responsive drug delivery has attracted most attention owing to the intracellular reductive environment, such as the high concentration of glutathione reductase in many cancer cells. Herein, a glutathione sensitive drug delivery nanoplatform was constructed by using core-shell mesoporous silica nanocomposite (Fe3O4@mSiO2) as carrier. By a simple silane coupling reaction, the glutathione cleavable diselenide linker has been prepared and grafted on to Fe3O4@mSiO2 to insure the encapsulation of anticancer drug doxorubicin. The detail release kinetics studies reveal the glutathione triggered drug release, which could be further adjusted by varying the amount of diselenide linker. To improve the tumor-targeting, folic acid was grafted. The cellular uptake and drug release investigation was carried out using HeLa (cervical cancer cell line) as the model cancer cell and L02 and HUVEC (human hepatic cell line and human umbilical vein endothelial cells, non-cancerous cell lines) as control, indicating the enhanced cytotoxicity toward HeLa cells that benefits from the fast endocytosis and enhanced cellular drug release owing to their overexpressing folic acid receptors and high concentration of glutathione. Associating with the magnetic targeting, these novel nanomaterials are expected to be promising in the potential application of tumor-targeting therapy.
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China.
Na
N
An
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China. Electronic address: linhuiming@hrbnu.edu.cn.
Huiming
H
Lin
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China.
Chunyu
C
Yang
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China.
Ting
T
Zhang
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China.
Ruihan
R
Tong
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China.
Yuhua
Y
Chen
College of Chemistry and Chemical Engineering, Harbin Normal University, Harbin 150025, PR China. Electronic address: qufengyu@hrbnu.edu.cn.
Fengyu
F
Qu
D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D012822:Silicon Dioxide; D004317:Doxorubicin; D005978:Glutathione; D052203:Ferrosoferric Oxide
Core-shell nanoparticles; Drug-delivery; Enzyme-triggered; Mesoporous silica; Targeting