Single step reconstitution of multifunctional high-density lipoprotein-derived nanomaterials using microfluidics.
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.
David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
YongTae
Y
Kim
Francois
F
Fay
David P
DP
Cormode
Brenda L
BL
Sanchez-Gaytan
Jun
J
Tang
Elizabeth J
EJ
Hennessy
Mingming
M
Ma
Kathryn
K
Moore
Omid C
OC
Farokhzad
Edward Allen
EA
Fisher
Willem J M
WJ
Mulder
Robert
R
Langer
Zahi A
ZA
Fayad
D000818:Animals; D002784:Cholesterol / Q000737:chemistry; D003198:Computer Simulation; D004337:Drug Carriers; D005290:Ferric Compounds / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006046:Gold / Q000737:chemistry; D008075:Lipoproteins, HDL / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008264:Macrophages; D008279:Magnetic Resonance Imaging; D051379:Mice; D044085:Microfluidics; D008856:Microscopy, Fluorescence; D008962:Models, Theoretical; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D045663:Quantum Dots; D019821:Simvastatin / Q000008:administration & dosage; D013927:Thrombosis / Q000473:pathology; D014057:Tomography, X-Ray Computed; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D005290:Ferric Compounds; D005456:Fluorescent Dyes; D008075:Lipoproteins, HDL; D014409:Tumor Necrosis Factor-alpha; C000499:ferric oxide; D006046:Gold; D002784:Cholesterol; D019821:Simvastatin