LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque

Christian A. Boada, Assaf Zinger, Scott Rohen, Jonathan O. Martinez, Michael Evangelopoulos, Roberto Molinaro, Madeleine Lu, Ramiro Alejandro Villarreal-Leal, Federica Giordano, Manuela Sushnitha, Enrica De Rosa, Jens B. Simonsen, Sergey Shevkoplyas, Francesca Taraballi*, Ennio Tasciotti

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach. The synthesized aposomes had a diameter of 91 ± 4 nm and a neutral surface charge of 0.7 mV ± mV. Protein analysis using western blot and flow cytometry confirmed the presence of apoB-100 on the nanoparticle’s surface. Furthermore, Aposomes retained liposomes’ drug loading capabilities, demonstrating a prolonged release curve with ∼80% cargo release at 4 hours. Considering the natural tropism of LDL towards the atherosclerotic plaques, we evaluated the biological properties of aposomes in a mouse model of advanced atherosclerosis. We observed a ∼20-fold increase in targeting of plaques when comparing aposomes to control liposomes. Additionally, aposomes presented a favorable biocompatibility profile that showed no deviation from typical values in liver toxicity markers (i.e., LDH, ALT, AST, Cholesterol). The results of this study demonstrate the possibilities of using apolipoprotein-based approaches to create nanoparticles with active targeting capabilities and could be the basis for future cardiovascular therapies.

Original languageEnglish
Article number794676
JournalFrontiers in Bioengineering and Biotechnology
Volume9
Number of pages14
ISSN2296-4185
DOIs
Publication statusPublished - 2021

Keywords

  • Apolipoprotein
  • Atherosclerosis
  • Drug Delivery
  • LDL
  • Liposome
  • Nanoparticle
  • Rapamycin

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