Three-dimensional hydrodynamic focusing method for polyplex synthesis

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  • Mengqian Lu, Department of Engineering Science and Mechanics, The Pennsylvania State University
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  • Yi-Ping Ho, Department of Biomedical Engineering, Duke University, Denmark
  • Christopher L Grigsby, Department of Biomedical Engineering, Duke University
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  • Ahmad Ahsan Nawaz, Department of Engineering Science and Mechanics, The Pennsylvania State University
  • ,
  • Kam W Leong, Department of Biomedical Engineering, Duke University
  • ,
  • Tony Jun Huang, Department of Engineering Science and Mechanics, The Pennsylvania State University
Successful intracellular delivery of nucleic acid therapeutics relies on multiaspect optimization, one of which is formulation. While there has been ample innovation on chemical design of polymeric gene carriers, the same cannot be said for physical processing of polymer-DNA nanocomplexes (polyplexes). Conventional synthesis of polyplexes by bulk mixing depends on the operators' experience. The poorly controlled bulk mixing process may also lead to batch-to-batch variation and consequent irreproducibility. Here, we synthesize polyplexes by using a three-dimensional hydrodynamic focusing (3D-HF) technique in a single-layered, planar microfluidic device. Without any additional chemical treatment or postprocessing, the polyplexes prepared by the 3D-HF method show smaller size, slower aggregation rate, and higher transfection efficiency, while exhibiting reduced cytotoxicity compared to the ones synthesized by conventional bulk mixing. In addition, by introducing external acoustic perturbation, mixing can be further enhanced, leading to even smaller nanocomplexes. The 3D-HF method provides a simple and reproducible process for synthesizing high-quality polyplexes, addressing a critical barrier in the eventual translation of nucleic acid therapeutics.
Original languageEnglish
JournalACS Nano
Volume8
Issue1
Pages (from-to)332-9
Number of pages8
ISSN1936-0851
DOIs
Publication statusPublished - 28 Jan 2014

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