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

• Published in: Frontiers in bioengineering and biotechnology Vol. 9; p. 794676
• Main Authors: Boada, Christian A, Zinger, Assaf, Rohen, Scott, Martinez, Jonathan O, Evangelopoulos, Michael, Molinaro, Roberto, Lu, Madeleine, Villarreal-Leal, Ramiro Alejandro, Giordano, Federica, Sushnitha, Manuela, De Rosa, Enrica, Simonsen, Jens B, Shevkoplyas, Sergey, Taraballi, Francesca, Tasciotti, Ennio
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 01.12.2021
• Subjects: Apolipoprotein; Bioengineering and Biotechnology; Drug Delivery; LDL; Liposome; Nanoparticle; Rapamycin; LDL; Nanoparticle; Atherosclerosis; Liposome; Rapamycin; Apolipoprotein; Drug Delivery
• ISSN: 2296-4185; 2296-4185
• DOI: 10.3389/fbioe.2021.794676

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.