Combined using of paclitaxel and salinomycin active targeting nanostructured lipid carriers against non-small cell lung cancer and cancer stem cells

Drug Delivery

Lixin Cao¹  Shanshan Jin²  Li Fan³  Chunrong Yang⁴  Jianwen Zhou⁵  Wenquan Zhu⁶  Cuiyan Han⁶  Xiaoyu Sui⁶  Mingshuang Sun⁷ 

[1] Department of Orthopedics, the First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Chin;Department of Pharmaceutical Preparations, Beijing Dezhong Wanquan Medicine Technology Co., Ltd, Beijing, China;Research Institute of Medicine & Pharmacy, Qiqihar Medical University, Qiqihar, China;School of Pharmacy, Jiamusi University, Jiamusi, China;School of Pharmacy, Jiamusi University, Jiamusi, China;School of Pharmacy, Qiqihar Medical University, Qiqihar, China;School of Pharmacy, Qiqihar Medical University, Qiqihar, China;School of Pharmacy, Taishan Medical University, Taian, China;

关键词: Nanostructured lipid carriers;    salinomycin;    paclitaxel;    combined therapy;    active targeting;   

DOI  :  10.1080/10717544.2019.1580799

来源: publisher

【 摘 要 】

The existing of avidity cancer stem cells (CSCs) made it an optical strategy to kill cancer cells and CSCs at the same time. Here, we constructed a CSCs specific nanocarrier naming T-S-NLC using the CD133+ targeting peptide TISWPPR (TR) as the targeting moiety attached to the distal end of PEG on salinomycin (Sal) loaded nanostructured lipid carriers (NLC), its pharmaceutical characteristics proved it 128.73 ± 2.09 nm, anionic spheroid with sustained release profile. It's in vitro targeting effect in CD133+ CSCs indicated that it exhibited superior CSCs internalization over non-modified NLC or free drug. Afterwards, it was used in combination with previously designed EGFR specific A-P-NLC (AEYLR peptide-PEG-modified paclitaxel loaded NLC) to achieve the goal to kill the cancer cells and CSCs, simultaneously. The in vitro tumor targeting effect of T-S-NLC + A-P-NLC was affirmed by cellular uptake and proliferation inhibition effect in NCI-H1299 and S180 cell lines showing advanced results over single preparation groups. In vivo tumor targeting effect in S180 tumor-bearing mice also validated the better tumor accumulative effect of the combined group. Last but not least, the in vivo antitumor effect strongly identified the greater tumor suppression effect of T-S-NLC + A-P-NLC than single preparation groups or combined use of free drugs while maintaining a good living state of the mice. To sum up, the combined usage of PTX and Sal active targeting NLC naming A-P-NLC + T-S-NLC which killed cancer cells and CSCs at the same time was a promising drug delivery system.

【 授权许可】

CC BY