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Dean flow and Dean instability play an important role in inertial microfluidics, with a wide application in mixing and sorting. However, most studies are limited to Dean flow in the microscale. This work first reports the application of Dean instability on organic nanoparticles synthesis at <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>D</mi><mi>e</mi></mrow></semantics></math></inline-formula> up to 198. The channel geometry (the tortuous channel) is optimized by simulation, in which the mixing efficiency is considered. With the optimized design, prednisolone nanoparticles are synthesized, and the size of the most abundant prednisolone nanoparticles is down to 100 nm with an increase in the <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>R</mi><mi>e</mi></mrow></semantics></math></inline-formula> and <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>D</mi><mi>e</mi></mrow></semantics></math></inline-formula> and smallest size down to 46 nm. This work serves as an ice-breaker to the real application of Dean instability by demonstrating its ability in mixing and nanomaterials like nanoparticle synthesis.