Synthesis of multicompartmental polymer nanoparticles enabling regulation of cross-compartmental cascade reactions

We construct multicompartmental nanoparticles with tunable compositions and sizes. • Nanoparticles quantitatively and positionally load multi-enzymes in compartments. • Enzyme amount and distribution regulate cross-compartmental cascade reactions. • Cross-compartmental cascade reasons manipulate and modulate particle locomotion. • Cell-mimetic nanoparticles show potential as microreactors or micromotors. The cell-mimetic multicompartment-in-compartment architecture holds considerable potential for many applications. However, customizing sub-micron multicompartmental colloidal systems capable of spatiotemporal control over signaling cascade and energy transmission across internal compartmentalized domains remains challenging. Herein, we report on a continuous nanoprecipitation-based tandem/parallel combined process to induce a multistage assembly, including polymer aggregation, nanoparticle aggregation and polymer deposition, to spontaneously form multicompartmental polymer nanoparticles with tuneable compositions and dimensions. This general and straightforward approach enables the controllable construction of homogeneous or heterogeneous internal compartments in multicompartmental nanoparticles and allows quantitative loading of diverse cargos (e.g., proteins, dyes) with precise localization within distinct compartmentalized domains (internal compartments or intermembrane space). With selective encapsulation of multiple enzymes in designated compartments, the multicompartment-in-compartment nanostructuration could conveniently control chemical signaling transduction across compartmentalized domains, thereby achieving effective regulation of cross-compartmental enzymatic cascade reactions in multicompartmental nanoparticles. This cell-mimetic multicompartmental colloidal system could perceive surrounding chemical signaling (e.g., glucose) and carry out cascade reaction-triggered energy transmission across its multi-organelle-like compartments for the controllable execution of self-generated chemical gradient-driven autonomous movement. This work provides a robust strategy for designing and constructing versatile multicompartmental colloidal materials with tailorable properties and functions, showing appealing potential for application in various fields. Download: Download high-res image (191KB) Download: Download full-size image