scFv-Anti-LDL(-)-Metal-Complex Multi-Wall Functionalized-Nanocapsules as a Promising Tool for the Prevention of Atherosclerosis Progression

Author(s):Show less -

Cavalcante, Marcela Frota ^[1] ; Adorne, Marcia Duarte ^[2] ; Turato, Walter Miguel ^[1] ; Kemmerer, Marina ^[3] ; Uchiyama, Mayara Klimuk ^[4] ; Cavazzin Asbahr, Ana Carolina ^[2] ; Soares Alves, Aline de Cristo ^[5] ; Poliselli Farsky, Sandra Helena ^[1] ; Drewes, Carine ^[1] ; Spatti, Marina Cecilia ^[1] ; Kazuma, Soraya Megumi ^[1] ; Boss, Marcel ^[3] ; Guterres, Silvia Staniscuaski ^[5] ; Araki, Koiti ^[4] ; Bruene, Bernhard ^[3] ; Namgaladze, Dmitry ^[3] ; Pohlmann, Adriana Raffin ^[2] ; Parra Abdalla, Dulcineia Saes ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[2] Univ Fed Rio Grande do Sul, Chem Inst, Dept Organ Chem, Porto Alegre, RS - Brazil

^[3] Goethe Univ Frankfurt, Fac Med, Inst Biochem 1, Frankfurt - Germany

^[4] Univ Sao Paulo, Dept Fundamental Chem, Inst Chem, Sao Paulo - Brazil

^[5] Univ Fed Rio Grande do Sul, Fac Pharm, Dept Prod & Control Med, Porto Alegre, RS - Brazil

• Document type: Journal article
• Source: FRONTIERS IN MEDICINE; v. 8, APR 20 2021.
• Web of Science Citations: 0

Abstract

Atherosclerosis can be originated from the accumulation of modified cholesterol-rich lipoproteins in the arterial wall. The electronegative LDL, LDL(-), plays an important role in the pathogenesis of atherosclerosis once this cholesterol-rich lipoprotein can be internalized by macrophages, contributing to the formation of foam cells, and provoking an immune-inflammatory response. Herein, we engineered a nanoformulation containing highly pure surface-functionalized nanocapsules using a single-chain fragment variable (scFv) reactive to LDL(-) as a ligand and assessed whether it can affect the LDL(-) uptake by primary macrophages and the progression of atherosclerotic lesions in Ldlr(-/-) mice. The engineered and optimized scFv-anti-LDL(-)-MCMN-Zn nanoformulation is internalized by human and murine macrophages in vitro by different endocytosis mechanisms. Moreover, macrophages exhibited lower LDL(-) uptake and reduced mRNA and protein levels of IL1B and MCP1 induced by LDL(-) when treated with this new nanoformulation. In a mouse model of atherosclerosis employing Ldlr(-/-) mice, intravenous administration of scFv-anti-LDL(-)-MCMN-Zn nanoformulation inhibited atherosclerosis progression without affecting vascular permeability or inducing leukocytes-endothelium interactions. Together, these findings suggest that a scFv-anti-LDL(-)-MCMN-Zn nanoformulation holds promise to be used in future preventive and therapeutic strategies for atherosclerosis. (AU)

• FAPESP's process: 12/51316-5 - Study of the activity of biodrugs, PPARs agonists and natural products with therapeutic potential in atherosclerosis
• Grantee: Dulcineia Saes Parra Abdalla
• Support Opportunities: Research Projects - Thematic Grants