Department of Microbiology, Center for Advanced Medical Education by BK21 Project, College of Medicine, Inha University, Incheon, Korea.
Int J Hyperthermia. 2011;27(7):698-707. doi: 10.3109/02656736.2011.608217.
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.
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.
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.
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.
我们研究了利用热疗来提高载多柔比星介孔硅纳米容器 Si-SS-CD-PEG 的抗癌疗效。假设是热量刺激谷胱甘肽介导的环糊精门卫降解，从而导致载体中多柔比星的释放和多柔比星诱导的细胞死亡。
通过评估 DOX 荧光强度的变化来研究载 DOX 的 Si-SS-CD-PEG 在含有谷胱甘肽 (GSH) 的 PBS 中的 DOX 释放情况。用共聚焦显微镜确定 42°C 加热对细胞内载体中 DOX 释放的影响。测定载 DOX 的 Si-SS-CD-PEG 引起的克隆形成和凋亡细胞死亡的程度。
只有在悬浮液中存在 GSH 时，DOX 才会从载 DOX 的 Si-SS-CD-PEG 中释放出来，而 42°C 的加热略微增加了载体中 DOX 的释放。加热显着增加了 A549 细胞中的 GSH 含量，并增加了内化载体中 DOX 的释放。加热载药载体处理的癌细胞显着增加了克隆形成死亡和细胞凋亡。A549 细胞中的 GSH 含量高于 L-132 细胞，并且在 37°C 和 42°C 下，A549 细胞对载 DOX 的 Si-SS-CD-PEG 的敏感性均远高于 L-132 细胞。
热疗增加了 DOX 从载 DOX 的 Si-SS-CD-PEG 中通过 GSH 介导的释放。此外，热疗显着增加了癌细胞中的 GSH 含量，从而增加了内化载体中 DOX 的释放，并增强了 DOX 诱导的克隆形成和凋亡细胞死亡。
