Yolk-shell nanovesicles endow glutathione-responsive concurrent drug release and T₁ MRI activation for cancer theranostics

The effort of incorporating therapeutic drugs with imaging agents has been one of the mainstreams of nanomedicine, which holds great promise in cancer treatment in terms of monitoring therapeutic drug activity and evaluating prognostic index. However, it is still technically challenging to develop nanomedicine endowing a spatiotemporally controllable mechanism of drug release and activatable imaging capability. Here, we developed a yolk-shell type of GSH-responsive nanovesicles (NVs) in which therapeutic drug (Doxorubicin, DOX) and magnetic resonance imaging (MRI) contrast agent (ultrasmall paramagnetic iron oxide nanoparticles, USPIO NPs) formed complexes (denoted as USD) and were encapsulated inside the NVs. The formation of USD complexes is mediated by both the electrostatic adsorption between DOX and poly(acrylic acid) (PAA) polymers and the DOX-iron coordination effect on USPIO NPs. The obtained USD NVs showed a unique yolk-shell structure with restrained drug activity and quenched T₁ MRI contrast ability which, on the other hand, can respond to glutathione (GSH) and lead to drug release and T₁ contrast activation in a spatiotemporally concurrent manner. Furthermore, the USD NVs exhibited great potential to kill HCT116 cancer cells in vitro and effectively inhibit the tumor growth in vivo. This study may shed light on the design of sophisticated nanotheranostics in precision nanomedicine.