Uniform hydrogel microparticles with ZIF-8 nanoparticles for molecular co-confinement of cascade enzymes are developed by microfluidics to achieve enhanced stability and reusability under harsh conditions.

Sub‐10 nm nanoparticles are known to exhibit extraordinary size‐dependent properties for wide applications. Many approaches have been developed for synthesizing sub‐10 nm inorganic nanoparticles, but the fabrication of sub‐10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub‐10 nm nanodroplets for template synthesis of sub‐10 nm polymeric nanoparticles is proposed. This strategy introduces a high‐concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular‐level impact on interfacial instability for creating sub‐10 nm nanoemulsions via self‐burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub‐10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand‐new opportunities to easily create sub‐10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.