Microfluidic Synthesis of Rigid Nanovesicles for Hydrophilic Reagents Delivery

We present a hollow‐structured rigid nanovesicle (RNV) fabricated by a multi‐stage microfluidic chip in one step, to effectively entrap various hydrophilic reagents inside, without complicated synthesis, extensive use of emulsifiers and stabilizers, and laborious purification procedures. The RNV contains a hollow water core, a rigid poly (lactic‐co‐glycolic acid) (PLGA) shell, and an outermost lipid layer. The formation mechanism of the RNV is investigated by dissipative particle dynamics (DPD) simulations. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside the hollow water core of RNV is ≈90 %. In comparison with the combination of free Dox and siRNA, RNV that co‐encapsulate siRNA and doxorubicin (Dox) reveals a significantly enhanced anti‐tumor effect for a multi‐drug resistant tumor model. Nanocarriers made easy: A multistage microfluidic chip is adopted for the one‐step synthesis of water core/PLGA shell/lipid layer rigid nanovesicles (RNVs) and effective entrapment of various kinds of hydrophilic reagents. An enhanced anti‐tumor effect is observed by co‐delivering siMDR1 and Dox using RNVs in both in vitro and in vivo experiments.