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The cellular uptake on FR positive A549 cells and negative L929 cells of FANP after pretreated with DTX was studied.

Furthermore, the cellular uptake on DTX pretreated cells of FA modified liposome (FA-LIP) was set as control to clarify this universal mechanism.

S3), confirming FANP could bind to FR on cell membrane and lead to enhanced cellular uptake by endocytosis, thus we evaluated the influence of DTX on cellular uptake of NP and FANP (Fig. The cellular uptake after pretreated with DTX was obviously enhanced in comparison with the control group and showed positive correlation with the concentration of DTX on A549 cells and U87 cells, implying that DTX could facilitate cellular internalization of NP.

More importantly, the cellular uptake of FANP increased after pretreated with DTX, displaying the superiority of combinatorial therapy between active tumor targeting and DTX pretreatment.

However, current studies didn’t investigate the internalization of targeted NP in different cell cycle phases.