Distinct Morphological Transitions of Photoreactive and Thermoresponsive Vesicles for Controlled Release and Nanoreactors

The construction of intelligent vesicular nanocarriers and nanoreactors has received increasing interests due to their potential in mimicking natural counterparts such as cells and organelles. Herein, we report thermoresponsive and photoreactive vesicles could be fabricated from amphiphilic block copolymers (BCPs), poly(N-isopropylacrylamide)-b-poly(2-((((2-nitrobenzyl)oxy)carbonyl)amino)ethyl acrylate) (PNIPAM-b-PNBOCA), which were synthesized via consecutive reversible addition–fragmentation chain transfer (RAFT) polymerizations. The resulting BCPs self-assembled into vesicles when temperatures were lower than the lower critical solution temperature (LCST) of PNIPAM blocks (defined as LCST0). However, the resulting vesicles irreversibly formed collapsed vesicles upon temperature rise (T > LCST0), and a further temperature increase (T > Tagg,0) led to the formation of irregular aggregates of collapsed vesicles. On the other hand, upon UV irradiation, the initially hydrophobic PNBOCA bilayers underwent aminolysis-induced cross-linking and hydrophobic-to-hydrophilic transition, resulting in elevated LCST (defined as LCSTuv). Although the thermo-induced collapse of PNIPAM coronas (T > LCSTuv) and the formation of aggregates of cross-linked vesicles (T > Tagg,uv) were observed, the initially vesicular morphology could be restored when cooling to lower than LCSTuv, as opposed to irreversible morphological transition without UV irradiation. The vesicular assemblies were engineered as nanocarriers for both hydrophilic (doxorubicin hydrochloride, DOX) and hydrophobic (Nile red, NR) payloads. The corelease profiles could be delicately regulated by both temperature variations and UV irradiation. Interestingly, DOX release could be also regulated by thermo-induced vesicle collapse without recourse to UV irradiation or by near-infrared (NIR) irradiation-induced vesicle collapse in the presence of photothermal agents coloaded within vesicular interiors as a result of the relatively low glass transition temperature of PNBOCA blocks. Moreover, nanoreactors were constructed by loading glucose oxidase (GOx) into the aqueous interiors of the vesicles, allowing for activating fluorogenic reactions by UV irradiation and temperature change.