Nanoparticle-Assembled Vacuolated Coacervates Control Macromolecule Spatiotemporal Distribution to Provide a Stable Segregated Cell Microenvironment.

Abstract

Membraneless coacervate compartments in the intracellular and pericellular space mediate critical cellular functions. Developing synthetic coacervates that emulate the morphological, physical, and functional complexity of these natural coacervates is challenging but highly desirable. Herein, a generalizable nanoparticle assembly (NPA) strategy is developed, which is applicable to interactive core-shell nanoparticles with different chemical makeups, to fabricate vacuolated coacervates. The obtained NPA coacervates contain stable internal vacuoles to provide segregated microcompartments, which can mediate the spatially heterogeneous distribution of diverse macromolecules via restricted diffusion. It is further shown that the vacuolated NPA coacervates can harbor and retain macromolecular medium supplements to regulate the functions of cells encapsulated in vacuoles. Furthermore, the restricted macromolecule diffusion can be abolished on demand via the triggered coacervate-hydrogel transition, thereby altering the exposure of encapsulated cells to environmental factors. It is believed that the NPA strategy provides new insights into the design principles of hierarchical coacervates that hold promising potential for a wide array of biomedical applications.