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

Abstract

Abstract 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\u2009±\u20092.09\u2009nm, 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\u2009+\u2009A-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\u2009+\u2009A-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\u2009+\u2009T-S-NLC which killed cancer cells and CSCs at the same time was a promising drug delivery system.