Elucidating the structural organization of a novel low-density lipoprotein nanoparticle reconstituted with docosahexaenoic acid.
Low-density lipoprotein nanoparticles reconstituted with unesterified docosahexaenoic acid (LDL-DHA) is promising nanomedicine with enhanced physicochemical stability and selective anticancer cytotoxic activity. The unique functionality of LDL-DHA ultimately relates to the structure of this nanoparticle. To date, however, little is known about the structural organization of this nanoparticle. In this study chemical, spectroscopic and electron microscopy analyses were undertaken to elucidate the structural and molecular organization of LDL-DHA nanoparticles. Unesterified DHA preferentially incorporates into the outer surface layer of LDL, where in this orientation the anionic carboxyl end of DHA is exposed to the LDL surface and imparts an electronegative charge to the nanoparticles surface. This negative surface charge promotes the monodisperse and homogeneous distribution of LDL-DHA nanoparticles in solution. Further structural analyses with cryo-electron microscopy revealed that the LDL-DHA nanostructure consist of a phospholipid bilayer surrounding an aqueous core, which is distinctly different from the phospholipid monolayer/apolar core organization of plasma LDL. Lastly, apolipoprotein B-100 remains strongly associated with this complex and maintains a discrete size and shape of the LDL-DHA nanoparticles similar to plasma LDL. This preliminary structural assessment of LDL-DHA now affords the opportunity to understand the important structure-function relationships of this novel nanoparticle.
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Rohit S
RS
Mulik
Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Hui
H
Zheng
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Kumar
K
Pichumani
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
James
J
Ratnakar
Department of Cell Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Qiu-Xing
QX
Jiang
Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Internal Medicine Division of Liver and Digestive Diseases, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Electronic address: ian.corbin@utsouthwestern.edu.
Ian R
IR
Corbin
D004281:Docosahexaenoic Acids / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000737:chemistry*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013499:Surface Properties
D008077:Lipoproteins, LDL; D004281:Docosahexaenoic Acids
Cryo-EM; Lipoprotein; Nanostructure; Omega-3 fatty acid; Spectroscopy