A self-assembling nanomedicine of conjugated linoleic acid-paclitaxel conjugate (CLA-PTX) with higher drug loading and carrier-free characteristic

作者：Zhong, Ting; Yao, Xin; Zhang, Shuang; Guo, Yang; Duan, Xiao-Chuan; Ren, Wei; Huang, Dan; Yin, Yi-Fan; Zhang, Xuan^*

来源：Scientific Reports, 2016, 6(1): 36614.

DOI：10.1038/srep36614

• CANCER-THERAPY
• ANTICANCER ACTIVITY
• ANTITUMOR EFFICACY
• MODIFIED LIPOSOMES
• DELIVERY
• NANOPARTICLES
• PRODRUGS
• GLIOMA
• TUMORS
• CELLS

The main objective of this study was to demonstrate the proof-of-principle for the hypothesis that conjugated linoleic acid-paclitaxel conjugate (CLA-PTX), a novel fatty acid modified anti-cancer drug conjugate, could self-assemble forming nanoparticles. The results indicated that a novel self-assembling nanomedicine, CLA-PTX@PEG NPs (about 105 nm), with Cremophor EL (CrEL)-free and organic solvent-free characteristics, was prepared by a simple precipitation method. Being the ratio of CLA-PTX: DSPE-PEG was only 1:0.1 (w/w), the higher drug loading CLA-PTX@PEG NPs (about 90%) possessed carrier-free characteristic. The stability results indicated that CLA-PTX@PEG NPs could be stored for at least 9 months. The safety of CLA-PTX@PEG NPs was demonstrated by the MTD results. The anti-tumor activity and cellular uptake were also confirmed in the in vitro experiments. The lower crystallinity, polarity and solubility of CLA-PTX compared with that of paclitaxel (PTX) might be the possible reason for CLA-PTX self-assembling forming nanoparticles, indicating a relationship between PTX modification and nanoparticles self-assembly. Overall, the data presented here confirm that this drug self-delivery strategy based on self-assembly of a CLA-PTX conjugate may offer a new way to prepare nanomedicine products for cancer therapy involving the relationship between anticancer drug modification and self-assembly into nanoparticles.

• 出版日期2016-11-4
• 单位北京大学