title: Conjugation of dexamethasone to C60 for the design of an anti-inflammatory nanomedicine with reduced cellular apoptosis.
abstract: 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-C60 was significantly lower than that of free DEX. Flow cytometric studies revealed that incubation with DEX-C60 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-C60 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-C60, and promote its clinical applications.
authors.affiliation: Laboratory of Physical Biology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Sun
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Zhong
authors.forename: Jiye
authors.initials: J
authors.lastname: Shi
authors.forename: Chunhai
authors.initials: C
authors.lastname: Fan
authors.forename: Qing
authors.initials: Q
authors.lastname: Huang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003907:Dexamethasone / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D037741:Fullerenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine / Q000379:methods*; D011965:Receptors, Glucocorticoid / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D000893:Anti-Inflammatory Agents; D037741:Fullerenes; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; C069837:fullerene C60