Drug Delivery (Jan 2019)

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

  • Jianwen Zhou,
  • Mingshuang Sun,
  • Shanshan Jin,
  • Li Fan,
  • Wenquan Zhu,
  • Xiaoyu Sui,
  • Lixin Cao,
  • Chunrong Yang,
  • Cuiyan Han

DOI
https://doi.org/10.1080/10717544.2019.1580799
Journal volume & issue
Vol. 26, no. 1
pp. 281 – 289

Abstract

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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.

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