bm501296d_si_001.pdf (1.13 MB)

Spatiotemporal Monitoring Endocytic and Cytosolic pH Gradients with Endosomal Escaping pH-Responsive Micellar Nanocarriers

Download (1.13 MB)
journal contribution
posted on 10.11.2014, 00:00 by Jinming Hu, Guhuan Liu, Cheng Wang, Tao Liu, Guoying Zhang, Shiyong Liu
Endosomal escape is of crucial importance to increase the therapeutic efficacy for nanoparticle-based drug and gene delivery. It has been long presumed that pH-responsive polymeric nanocarriers are potent in aiding endosomal escape due to the “proton sponge” effect; however, the intracellular pH (pHi) gradients subjected by pH-responsive nanocarriers during endocytic and endosomal escaping processes remain to be quantified and elucidated. We herein report the fabrication of ultrasensitive ratiometric fluorescent pHi imaging probes with robust endosomal escaping capability derived from dual dye-labeled pH-responsive block copolymers, which can directly monitor endosomal escape in living cells and quantitatively measure pHi variations during the entire endocytic and endosomolytic processes. Micellar nanoparticle-based pHi sensors could be efficiently internalized into cells via endocytosis where micelle-to-unimer transition occurs, followed by endosomal escape into the cytosol. This process is accompanied by deactivation of blue coumarin emission within acidic organelles and restored blue/red dual emissions within the neutral cytosolic milieu, allowing for ratiometric fluorescent imaging of entire pHi gradients subjected by micellar nanoparticles following the endocytic transport pathway.

History

Exports