(Invited) Microfluidic Synthesis of Functional Nanomaterials

Abstract

The controlled synthesis of functional nanoparticles with tunable structures and properties has been extensively investigated for cancer treatment and diagnosis. Among a variety of methods for fabrication of nanoparticles, microfluidics-based synthesis enables enhanced mixing and precise fluidic modulation inside microchannels, thus allowing for the flow-mediated production of nanoparticles in a controllable manner. We present a hollow-structured rigid nanoparticle 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 nanoparticle contains a hollow water core, a rigid poly (lactic-co-glycolic acid) (PLGA) shell, and an outermost lipid layer. The entrapment efficiency of hydrophilic reagents such as calcein, rhodamine B and siRNA inside hollow water core is ~ 90 %. In comparison with the combination of free Dox and siRNA, the hollow-structured rigid nanoparticle that co-encapsulates siRNA and doxorubicin (Dox) reveals a significantly enhanced anti-tumor effect for a multi-drug resistant tumor model. Lipid-covered PLGA NPs or liposomes of the same size and surface properties, but different rigidity by controlling the interfacial water layer, can be realized using a two-stage microfluidic chip. It enables us to explore how rigidity of NPs regulates the cellular uptake and elucidate the intrinsic mechanism. Given the only significant difference between those two types of NPs is the rigidity, the experiments suggest that rigidity could dramatically alter the cellular uptake efficiency, with rigid NPs being easier to get through members than soft ones. The mechanisms revealed here suggest that tuning of rigidity of NPs is one appealing way in improving therapeutic efficiency.