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

Autor:	Boada CA; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States.; Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, México, Mexico., Zinger A; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States.; Department of Engineering Medicine, Texas A&M University, Houston, TX, United States.; Laboratory for Bioinspired NanoEngineering and Translational Therapeutics, Department of Chemical Engineering, Technion-Israel Institute of Technology, Haifa, Israel., Rohen S; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States., Martinez JO; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States., Evangelopoulos M; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States., Molinaro R; IRCCS Ospedale San Raffaele srl, Milan, Italy.; Department of Biomedical Engineering, University of Houston, Houston, TX, United States., Lu M; Department of Biomedical Engineering, University of Houston, Houston, TX, United States., Villarreal-Leal RA; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States.; Tecnológico de Monterrey, Escuela de Ingeniería y Ciencias, México, Mexico., Giordano F; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States.; Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, United States., Sushnitha M; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States., De Rosa E; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States., Simonsen JB; Department of Health Technology, Technical University of Denmark, Lyngby, Denmark., Shevkoplyas S; Department of Biomedical Engineering, University of Houston, Houston, TX, United States., Taraballi F; Regenerative Medicine Program, Houston Methodist Research Institute, Houston, TX, United States.; Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX, United States., Tasciotti E; San Raffaele University, Rome and IRCCS San Raffaele Hospital, Rome, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in bioengineering and biotechnology [Front Bioeng Biotechnol] 2021 Dec 01; Vol. 9, pp. 794676. Date of Electronic Publication: 2021 Dec 01 (Print Publication: 2021).
DOI:	10.3389/fbioe.2021.794676
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Boada, Zinger, Rohen, Martinez, Evangelopoulos, Molinaro, Lu, Villarreal-Leal, Giordano, Sushnitha, De Rosa, Simonsen, Shevkoplyas, Taraballi and Tasciotti.)
Databáze:	MEDLINE
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