Hyperbranched polymer micelles with triple-stimuli backbone-breakable iminoboronate ester linkages

Abstract Hyperbranched polymers have attracted increasing interests due to their unique structure-related advantages and have been utilized as drug carriers for controlled delivery. However, it is still challenging to prepare multi stimuli-responsive hyperbranched polymers to sense and response the complex yet delicate changes in physiological environment. Herein, we propose a triple-stimuli backbone-breakable hyperbranched polymer (HBP(OEG-IB)), which is prepared via the convenient iminoboronate multi-component reaction of α,ω-di(1,2-diol)s oligo(ethylene glycol), tris(3-aminopropyl)amine and 2-formylphenylboronic acid. Upon the stimulation of CO2, lactic acid and glutathione, micelles formed by HBP(OEG-IB) could be disrupted via the dissociation of iminoboronate ester bond to subsequent release incorporated camptothecin (CPT). Cell experiments show that the HBP(OEG-IB) is non-toxic but can enhance the therapeutic effect of CPT thanks to the effect of the protonated tertiary amino groups. The demonstration made in this work can enrich the design of responsive HBPs and can be readily applied to other systems with tunable responsive properties and functions.