Redox-Sensitive Citronellol–Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine

详细信息    查看全文

• 作者：Peng Xue ; Dan Liu ; Jing Wang ; Na Zhang ; Jiahua Zhou ; Lin Li ; Weiling Guo ; Mengchi Sun ; Xiangfei Han ; Yongjun Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：May 18, 2016
• 年：2016
• 卷：27
• 期：5
• 页码：1360-1372
• 全文大小：725K
• 年卷期：0
• ISSN：1520-4812

文摘

Citronellol-cabazitaxel (CIT-ss-CTX) conjugate self-assembled nanoparticles (CSNPs) were designed and prepared by conjugating cabazitaxel with citronellol via the disulfide bond that is redox-sensitive to the high concentration of glutathione within tumor cells. Notably, the CSNPs maintained in the cell cytotoxicity. Moreover, the AUC_0-t of CSNPs was 6.5-fold higher than that of cabazitaxel solutions and the t_1/2 was prolonged 2.3 times. Furthermore, we found that CSNPs could be employed as an efficient carrier for other hydrophobic drugs or imaging agents. Thus, the in vivo targeting study was implemented via using 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-loaded CSNPs as imaging agent, which showed CSNPs could effectively accumulate at the tumor site. Curcumin, a hydrophobic anticancer drug, was successfully loaded in CSNPs which exhibits good stability and synergistic antitumor effects. The citronellol–cabazitaxel conjugate therefore has a promising perspective as a multifunctional nanomedicine for combination therapy and theranostics attributed to its long-circulation property, redox-sensitive mechanism, and high drug coloading capability.