title: Hyperthermia improves therapeutic efficacy of doxorubicin carried by mesoporous silica nanocontainers in human lung cancer cells.
abstract: OBJECTIVE
  We investigated the use of hyperthermia to improve the anti-cancer efficacy of doxorubicin (DOX)-loaded mesoporous silica nanocontainer Si-SS-CD-PEG. The hypothesis was that heat stimulates glutathione-mediated degradation of cyclodextrin gatekeeper, thereby causing the release of DOX from the carrier and DOX-induced cell death.
  
  
  METHODS
  The release of DOX from DOX-loaded Si-SS-CD-PEG suspended in PBS containing glutathione (GSH) was studied by assessing the changes in DOX fluorescence intensity. The effect of heating at 42°C on the release of DOX from the intracellular carriers was determined with confocal microscopy. The extents of clonogenic and apoptotic cell death caused by DOX-loaded Si-SS-CD-PEG were determined.
  
  
  RESULTS
  The release of DOX from DOX-loaded Si-SS-CD-PEG in PBS occurred only when GSH presented in the suspension, and heating at 42°C slightly increased the release of DOX from the carriers. Heating significantly elevated the GSH content in A549 cells and increased the release of DOX from the internalised carriers. Heating the cancer cells treated with the carriers at 42°C markedly increased the clonogenic death and apoptosis. The GSH content in A549 cells was greater than that in L-132 cells, and A549 cells were far more sensitive than L-132 cells to DOX-loaded Si-SS-CD-PEG at both 37°C and 42°C.
  
  
  CONCLUSIONS
  Hyperthermia increased the GSH-mediated release of DOX from DOX-loaded Si-SS-CD-PEG. Furthermore, hyperthermia markedly elevated the GSH content in cancer cells, thereby increasing the release of DOX from the internalised carriers and potentiating the DOX-induced clonogenic and apoptotic cell death.
authors: Department of Microbiology, Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University, Incheon, Korea.
authors: Hyemi
authors: H
authors: Lee
authors: Saehee
authors: S
authors: Kim
authors: Bo-Hwa
authors: BH
authors: Choi
authors: Moon-Taek
authors: MT
authors: Park
authors: Jeonghun
authors: J
authors: Lee
authors: Seong-Yun
authors: SY
authors: Jeong
authors: Eun Kyung
authors: EK
authors: Choi
authors: Byung-Uk
authors: BU
authors: Lim
authors: Chulhee
authors: C
authors: Kim
authors: Heon Joo
authors: HJ
authors: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000077192:Adenocarcinoma of Lung; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003505:Cyclodextrins / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006979:Hyperthermia, Induced; D008175:Lung Neoplasms / Q000188:drug therapy*; D049329:Nanostructures / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D013388:Succinimides / Q000008:administration & dosage
chemical_list: D000903:Antibiotics, Antineoplastic; D003505:Cyclodextrins; D004337:Drug Carriers; D013388:Succinimides; D011092:Polyethylene Glycols; D004317:Doxorubicin; C050761:polyethylene glycol bis(succinimidyl succinate); D005978:Glutathione