Conjugation of Dexamethasone to C60 for the Design of an Anti-Inflammatory Nanomedicine with Reduced Cellular Apoptosis

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• 作者：Yi Zhang ; Lu Wang ; Yanhong Sun ; Ying Zhu ; Zengtao Zhong ; Jiye Shi ; Chunhai Fan ; Qing Huang
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2013
• 出版时间：June 12, 2013
• 年：2013
• 卷：5
• 期：11
• 页码：5291-5297
• 全文大小：406K
• 年卷期：v.5,no.11(June 12, 2013)
• ISSN：1944-8252

文摘

Dexamethasone (DEX) is a well-known anti-inflammatory drug, whose widespread clinical use is nevertheless restricted by its serious side effects. By conjugation of DEX with C₆₀, we found that this nanomedicine retained the anti-inflammatory activity of DEX while reducing side effects in the animal model. In mouse thymocytes, the CCK-8 assay showed that the cytotoxicity of DEX鈥揅₆₀ was significantly lower than that of free DEX. Flow cytometric studies revealed that incubation with DEX鈥揅₆₀ induced much less apoptotic thymocytes. Interestingly, such reduced cytotoxicity and apoptosis were not observed when equal moles of free C₆₀ and free DEX were coincubated with thymocytes, suggesting that the conjugation alters the signal pathway of DEX. Indeed, we found that the binding of DEX鈥揅₆₀ and a glucocorticoid receptor (GR) was partially blocked in the thymocytes, which resulted in down-regulation of several apoptosis-related genes. These findings help understand the mechanism of beneficial effects of this new nanomedicine, DEX鈥揅₆₀, and promote its clinical applications.

Keywords:

dexamethasone; C₆₀; glucocorticoid receptor; apoptosis; thymocytes