Controlled enzymatic reactions by programmed confinement in clusters of polymersomes and Janus nanoparticles

Compartmentalization is essential in nature for precisely controlling metabolic reactions, exchange of molecules and signals with the environment and inter-cell communication. While artificial organelles and cells offer simplified conditions for studying enzymatic reactions, it is still challenging to spatially and directionally control them. Here we present self-organized clusters combining catalytic nanocompartments (CNCs) loaded with different enzymes that are specifically attached to Janus nanoparticles (JNPs). The clusters are modularly assembled through programmed DNA hybridization. The asymmetry of the JNPs has unique advantages by allowing a precise arrangement of the CNCs and enabling, in a modular manner, various reaction configurations, including single, parallel and cascade enzymatic reactions. Additionally, JNP-CNCs clusters integrating imaging and therapeutic nanocompartments support nanotheranostic applications by simultaneous precise detection of their in vitro position and production of reactive oxygen species (ROS) that induce apoptosis. Such JNP-CNCs clusters provide both spatial and directional control of enzymatic reactions at the nanoscale and have high potential in biomedical applications, including protein therapy and theranostics.