Redox-Sensitive Citronellol-Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine
Redox-Sensitive Citronellol-Cabazitaxel Conjugate: Maintained in Vitro Cytotoxicity and Self-Assembled as Multifunctional Nanomedicine
复制标题
氧化还原敏感的香茅醇-卡巴他赛缀合物：维持体外细胞毒性并自组装为多功能纳米药物
DOI：
10.1021/acs.bioconjchem.6b00155
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发表时间：
2016-05-01
影响因子：
4.7
通讯作者：
Wang, Yongjun
中科院分区：
文献类型：
--
作者：
Xue, Peng;Liu, Dan;Wang, Yongjun
设计并制备了香茅醇-卡巴紫杉醇(CIT-ss-CTX)共轭自组装纳米粒(CSNPs)。值得注意的是，CSNPs在细胞内保持了细胞毒性。此外，CSNPs的AUC(0-t)是卡氮紫杉醇溶液的6.5倍，t(1/2)延长了2.3倍。此外，我们还发现CSNPs可以作为其他疏水药物或显像剂的有效载体。因此，体内靶向研究是通过使用1，1-dioctadecyl-3，3，3，3-tetramethylindotricarbocyanine碘(DIR)负载的CSNPs作为显像剂来实现的，结果表明CSNPs可以有效地在肿瘤部位聚集。将疏水性抗癌药物姜黄素成功地负载到CSNPs中，具有良好的稳定性和协同抗肿瘤作用。香茅醇卡氮紫杉醇结合物具有长循环特性、氧化还原敏感机制和较高的药物初生能力，因此作为一种多功能纳米药物用于联合治疗和治疗具有广阔的前景。
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.