title: Multicolored pH-tunable and activatable fluorescence nanoplatform responsive to physiologic pH stimuli.
abstract: Tunable, ultra-pH responsive fluorescent nanoparticles with multichromatic emissions are highly valuable in a variety of biological studies, such as endocytic trafficking, endosome/lysosome maturation, and pH regulation in subcellular organelles. Small differences (e.g., <1 pH unit) and yet finely regulated physiological pH inside different endocytic compartments present a huge challenge to the design of such a system. Herein, we report a general strategy to produce pH-tunable, highly activatable multicolored fluorescent nanoparticles using commonly available pH-insensitive dyes with emission wavelengths from green to near IR range. The primary driving force of fluorescence activation between the ON (unimer) and OFF (micelle) states is the pH-induced micellization. Among three possible photochemical mechanisms, homo Förster resonance energy transfer (homoFRET)-enhanced decay was found to be the most facile strategy to render ultra-pH response over the H-dimer and photoinduced electron transfer (PeT) mechanisms. Based on this insight, we selected several fluorophores with small Stoke shifts (<40 nm) and established a panel of multicolored nanoparticles with wide emission range (500-820 nm) and different pH transitions. Each nanoparticle maintained the sharp pH response (ON/OFF < 0.25 pH unit) with corresponding pH transition point at pH 5.2, 6.4, 6.9, and 7.2. Incubation of a mixture of multicolored nanoparticles with human H2009 lung cancer cells demonstrated sequential activation of the nanoparticles inside endocytic compartments directly correlating with their pH transitions. This multicolored, pH-tunable nanoplatform offers exciting opportunities for the study of many important cell physiological processes, such as pH regulation and endocytic trafficking of subcellular organelles.
authors.affiliation: Department of Pharmacology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Kejin
authors.initials: K
authors.lastname: Zhou
authors.forename: Haoming
authors.initials: H
authors.lastname: Liu
authors.forename: Shanrong
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Huang
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Baran D
authors.initials: BD
authors.lastname: Sumer
authors.forename: Jinming
authors.initials: J
authors.lastname: Gao
mesh_terms: D045744:Cell Line, Tumor; D004705:Endocytosis; D005453:Fluorescence; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000032:analysis*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008823:Micelles; D053758:Nanoparticles / Q000032:analysis*
chemical_list: D005456:Fluorescent Dyes; D008823:Micelles