posted on 2021-10-15, 16:04authored byDaniel
A. Paterson, Wye-Khay Fong, Sarah Hook, Allan B. Gamble
Block copolymers (BCPs) that can
self-assemble into particles and
be triggered by disease-specific molecules such as hydrogen sulfide
(H2S) have the potential to impact on drug delivery, decreasing
off-target toxicities while increasing drug efficacy. However, the
incorporation of H2S-responsive aryl azides into BCPs for
self-assembly has been limited by heat, light, and radical sensitivities.
In this study, a robust activator regenerated by the electron-transfer
atom-transfer radical polymerization reaction was used to synthesize
aryl-azide-containing BCPs under ambient conditions. Conditions controlling
self-assembly of the BCPs into 150–200 nm particles and the
physicochemical properties of the particles were investigated. The
use of nanoprecipitation with tetrahydrofuran to promote self-assembly
of the BCPs resulted in vesicle structures, while dimethylformamide
or dimethylsulfoxide resulted in polymeric bicontinuous nanospheres
(BCNs). Triggering of the BCPs and particles (vesicles or BCNs) via exposure to H2S revealed that unsubstituted
aryl azides were readily reduced (by HS–), resulting
in particle disruption or cross-linking. The relative polar nature
of the particle bilayers containing unsubstituted aryl azides and
the open structure of the BCNs did however limit encapsulation of
small hydrophilic and hydrophobic payloads. Incorporation of a benzylamide
substituent onto the aryl azide group increased the hydrophobicity
of the particles and encapsulation of hydrophilic cargo but reduced
sensitivity to H2S, likely due to the reduced penetration
of HS– into the bilayer.