한빛사논문
Massachusetts Institute of Technology, 현 Georgia Institute of Technology
Abstract
YongTae Kim†, Francois Fay ‡, David P. Cormode ‡, Brenda L. Sanchez-Gaytan ‡, Jun Tang ‡, Elizabeth J. Hennessy⊥ , Mingming Ma †, Kathryn Moore⊥ , Omid C. Farokhzad §, Edward Allen Fisher⊥ , Willem J. M. Mulder ‡∥, Robert Langer †*, and Zahi A. Fayad ‡*
† David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
‡ Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States
§ Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
⊥ Departments of Medicine (Cardiology) and Cell Biology, NYU School of Medicine, New York, New York 10016, United States
∥ Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands
*Address correspondence to Robert Langer, Zahi A. Fayad
Abstract
High-density lipoprotein (HDL) is a natural nanoparticle that transports peripheral cholesterol to the liver. Reconstituted high-density lipoprotein (rHDL) exhibits antiatherothrombotic properties and is being considered as a natural treatment for cardiovascular diseases. Furthermore, HDL nanoparticle platforms have been created for targeted delivery of therapeutic and diagnostic agents. The current methods for HDL reconstitution involve lengthy procedures that are challenging to scale up. A central need in the synthesis of rHDL, and multifunctional nanomaterials in general, is to establish large-scale production of reproducible and homogeneous batches in a simple and efficient fashion. Here, we present a large-scale microfluidics-based manufacturing method for single-step synthesis of HDL-mimicking nanomaterials (μHDL). μHDL is shown to have the same properties (e.g., size, morphology, bioactivity) as conventionally reconstituted HDL and native HDL. In addition, we were able to incorporate simvastatin (a hydrophobic drug) into μHDL, as well as gold, iron oxide, quantum dot nanocrystals or fluorophores to enable its detection by computed tomography (CT), magnetic resonance imaging (MRI), or fluorescence microscopy, respectively. Our approach may contribute to effective development and optimization of lipoprotein-based nanomaterials for medical imaging and drug delivery.
Keywords: HDL; multifunctional; nanoparticle; reconstitution; microfluidics; high-throughput
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