Remote Loading of Small‐Molecule Therapeutics into Cholesterol‐Enriched Cell‐Membrane‐Derived Vesicles

The increasing popularity of biomimetic design principles in nanomedicine has led to therapeutic platforms with enhanced performance and biocompatibility. This includes the use of naturally derived cell membranes, which can bestow nanocarriers with cell‐specific functionalities. Herein, we report on a strategy enabling efficient encapsulation of drugs via remote loading into membrane vesicles derived from red blood cells. This is accomplished by supplementing the membrane with additional cholesterol, stabilizing the nanostructure and facilitating the retention of a pH gradient. We demonstrate the loading of two model drugs: the chemotherapeutic doxorubicin and the antibiotic vancomycin. The therapeutic implications of these natural, remote‐loaded nanoformulations are studied both in vitro and in vivo using animal disease models. Ultimately, this approach could be used to design new biomimetic nanoformulations with higher efficacy and improved safety profiles.