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Abstract Nanocarriers are essential for targeted and enhanced drug delivery. However, the use of toxic solvent and the complex of chemical functionalization have seriously limited their clinical translation. Here, a one‐step strategy is developed to direct the self‐assembly of biocompatible core‐shell nanocapsules with tunable surface functionality by microfluidics. Upon rapid mixing and solvent exchange of ethanol with water in a microfluidic device, drug, oil, polymer, and polymer‐PEG‐function co‐precipitate and self‐assemble into core‐shell nanocapsules with desired surface functionality as driven by energy minimization. The prepared PCL‐PEG‐FA core‐shell nanocapsules demonstrate a high encapsulation efficiency and loading capacity and exhibit excellent tumor‐targeting drug delivery performances both in vitro and in vivo via the binding of functional group on the nanocapsule surface with corresponding receptor on the tumor cell membrane. The immune activation in the tumor microenvironment is investigated in detail by flow cytometry and multiplex immunohistochemistry staining to reveal the underlying mechanism for enhanced anti‐tumor performances. The developed strategy is green, facile, versatile, scalable and offers a promising platform for the design of advanced nanocarriers with hierarchical structure and desired function for enhanced drug delivery.
Yang et al. (Fri,) studied this question.