title: Spatiotemporal monitoring endocytic and cytosolic pH gradients with endosomal escaping pH-responsive micellar nanocarriers.
abstract: 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.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Department of Polymer Science and Engineering, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Hu
authors.forename: Guhuan
authors.initials: G
authors.lastname: Liu
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Guoying
authors.initials: G
authors.lastname: Zhang
authors.forename: Shiyong
authors.initials: S
authors.lastname: Liu
mesh_terms: D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D008823:Micelles