Temperature-sensitive poly(phenyleneethynylene) nanomedicines for intracellular tracking via fluorescence resonance energy transfer

pNIPAM-grafted poly(phenyleneethynylene) nanoparticles (pNE NPs) were synthesized by the atom transfer radical polymerization and Sonogashira coupling reaction and were developed as novel self-indicating drug nano-carriers for monitoring the intracellular drug release in the present work. Owing to the strong π–π stacking and hydrophobic interaction between pNE NPs and Dox, the drug loading amount (DL) and encapsulation efficiency (EE) reached up to 19.9% and 99.2%, respectively. The resultant doxorubicin-loaded pNE NPs (Dox-pNE NPs) achieved fluorescence resonance energy transfer (FRET) from the green fluorescence of PPEs (λem = 485 nm) to the red fluorescence of Dox (λem = 556 nm), which was used to monitor the intracellular release of Dox. The intracellular behavior of Dox-pNE NPs indicated that the green fluorescence of PPEs was gradually enhanced and the red fluorescence of Dox was correspondingly reduced after Dox-pNE NPs were taken up into the cells. It meant that the FRET effect could be characterized by the relative ratio of the green and red fluorescence intensities, which was significantly reduced with the increase in cell culture time. In addition, a long-term sustained release of Dox from Dox-pNE NPs was also studied in vitro at various pHs by monitoring the FRET effect. In conclusion, pNE NPs could be promising novel self-indicating nano-carriers for monitoring drug intracellular release.