Crosslinked pH-responsive polymersome via Diels-Alder click chemistry: A reversible pH-dependent vesicular nanosystem

Herein, we have developed pH-responsive shape-persistent polymersomes made of well-defined amphiphilic
poly(ethylene oxide)-block-poly(diisopropylaminoethyl methacrylate-co-furfuryl methacrylate)s PEO-b-P(DPAco-
FMA) by exploiting Diels-Alder chemistry as a robust and simple crosslinking method. Using Photo-induced
Copper Mediated Reversible Deactivation Radical Polymerization, we synthesized PEO-b-P(DPA-co-FMA) with
optimal block ratios that favor the formation of polymersomes in aqueous media having pH-responsive P(DPAco-
FMA) membranes. Owing to the existence of furfuryl pendant groups within the polymersome membranes,
the crosslinking of pH-responsive P(DPA-co-FMA) chains can be achieved via Diels-Alder chemistry.
Interestingly, the resulting crosslinked polymersomes swell when the pH in the solution is decreased so that it
lies in a biologically relevant range, as was demonstrated by cryogenic transmission electron microscopy. Here,
the polymersomes' ability to swell can be controlled by adjusting the amount of crosslinker. A minimum
threshold of crosslinking density is needed for the polymersomes to swell while an excess amount of crosslinker
quenched their ability to swell. Furthermore, crosslinked polymersomes are capable of encapsulating hydrophilic
model drug, such as Rhodamine B. At pH 7.20, due to the compact and hydrophobic membrane, the
diffusion of the dye from the interior of the polymersomes to the media is minimized, while the pronation of
PDPA at an acidic pH of 4.00, enables a permeable membrane, allowing the loaded cargo to leak much more
quickly. The shape-persistent polymersomes that we developed herein, are a promising nano-platform for use in
drug delivery applications.