Response of heterogeneous cancer cells on targeted nanoparticles

Heterogenous cancer cells possess cancer multidrug resistance (MDR) due to their relative quiescence and ABC-transporter expression. Heterogenous cancer cells can be detected by an Rh123 exclusion assay for identifying Rh123low population. In the present study, we fabricated targeted nanoparticles entrapped with Rh123 (Rh123 NPs) to investigate the effect of these targeted nanoparticles on an Rh123low population. The Rh123low population stained by Rh123 NPs exhibited similar heterogeneity to that stained by Rh123. In addition, the ABC-transporters did not contribute to the uptake of Rh123 or Rh123 NPs. Interestingly, ABC-transporters in the Rh123low population stained by Rh123 were possibly responsible for Rh123 efflux, while Rh123 NPs were not susceptible to ABC-transporters in the Rh123low population. It is plausible that the synergistic effect of NPs caused a targeted and endocytic effect which promoted the cellular uptake of Rh123 NPs, and the targeted effect played a more important role.