Engineering Intracellular Delivery Nanocarriers and Nanoreactors from Oxidation-Responsive Polymersomes via Synchronized Bilayer Cross-Linking and Permeabilizing Inside Live Cells

• DOI: 10.1021/jacs.6b04115
• Publication Date: 2016-08-03T10:55:07Z
• Authors: Zhengyu Deng; Yinfeng Qian; Yongqiang Yu; Guhuan Liu; Jinming Hu; Guoying Zhang; Shiyong Liu
• Keywords: Polymersome; Nanoreactor; Nanocarriers

Reactive oxygen species (ROS) and oxidative stress are implicated in various physiological pathological processes, this feature provides a vital biochemical basis for designing novel therapeutic diagnostic nanomedicines. Among them, oxidation-responsive micelles vesicles (polymersomes) of amphiphilic block copolymers have been extensively explored; however, previous works, oxidation by ROS including H2O2 exclusively leads to microstructural destruction polymeric assemblies. For polymersomes, fast release encapsulated hydrophilic drugs bioactive macromolecules will occur upon disintegration. Under certain application circumstances, does not meet design requirements sustained-release drug nanocarriers long-acting vivo nanoreactors. Also note that conventional polymersomes possess thick hydrophobic bilayers compromised membrane permeability, rendering them as ineffective We herein report the fabrication multifunctional exhibiting intracellular milieu-triggered vesicle bilayer cross-linking, permeability switching, enhanced imaging/drug features. Mitochondria-targeted reactive were obtained through self-assembly containing arylboronate ester-capped self-immolative side linkages block, followed surface functionalization with targeting peptides. Upon cellular uptake, triggers cascade decaging reactions generates primary amine moieties; prominent amidation reaction then occurs within membranes, resulting concurrent cross-linking hydrophobic-to-hydrophilic transition polymersome inside live cells. This process was further utilized achieve integrated functions such sustained release, (combination) chemotherapy monitored fluorescence magnetic resonance (MR) imaging turn-on, construct fluorogenic nanoreactors cytosolic thiol-containing molecules.