A Facile Fabrication of Lysosome-Targeting pH Fluorescent Nanosensor Based on PEGylated Polyester Block Copolymer

Abstract

A novel lysosome-targeting PEGylated polyester-based fluorescent pH nanosensor is fabricated by the combination of ring-opening copolymerization (ROCOP), side-group modification and subsequent self-assembly. First, a key target amphiphilic copolymer carrier for rhodamine (Rh) pH indicator is synthesized in a facile manner by the ROCOP of phthalic anhydride with allyl glycidyl ether using mPEG-OH and t-BuP1/Et3B as the macroinitiator and binary catalyst, respectively. Subsequently, Rh moieties are covalently attached on the polymer chain with controllable grafting degree via an efficient thiol-ene click reaction. Concurrently, the effect of catalyst systems and reaction conditions on the catalytic copolymerization performance is presented, and the quantitative introduction of Rh is described in detail. Owing to its amphiphilic characteristics, the rhodamine-functionalized polyester-based block copolymer can self-assemble into micelles. With the covalent incorporation of Rh moieties, the as-formed micelles exhibit excellent absorption and fluorescence-responsive sensitivity and selectivity towards H+ in the presence of various metal cations. Moreover, the as-prepared micelles with favorable water dispersibility, good pH sensitivity and excellent biocompatibility also display appreciable cell-membrane permeability, staining ability and pH detection capability for lysosomes in living cells. This work provides a new strategy for the facile synthesis of novel biocompatible polymeric fluorescent pH nanosensors for the fluorescence imaging of lysosomal pH changes.