TY  - JOUR
A1  - Cavalcante, Marcela Frota
A1  - Adorne, Márcia Duarte
A1  - Turato, Walter Miguel
A1  - Kemmerer, Marina
A1  - Uchiyama, Mayara Klimuk
A1  - Asbahr, Ana Carolina Cavazzin
A1  - Alves, Aline de Cristo Soares
A1  - Farsky, Sandra Helena Poliselli
A1  - Drewes, Carine
A1  - Spatti, Marina Cecília
A1  - Kazuma, Soraya Megumi
A1  - Boß, Marcel
A1  - Guterres, Silvia Stanisçuaski
A1  - Araki, Koiti
A1  - Brüne, Bernhard
A1  - Namgaladze, Dmitry
A1  - Pohlmann, Adriana Raffin
A1  - Abdalla, Dulcineia Saes Parra
T1  - scFv-Anti-LDL(-)-Metal-Complex Multi-Wall Functionalized-Nanocapsules as a Promising Tool for the Prevention of Atherosclerosis Progression
T2  - Frontiers in medicine
N2  - 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.
KW  - atherosclerosis
KW  - nanocapsules
KW  - electronegative LDL
KW  - macrophage
KW  - single chain fragment variable
KW  - nanoformulation
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62038
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-620387
SN  - 2296-858X
N1  - This research was supported by FAPESP (São Paulo Research Foundation, grant 2012/51316-5 to DA and scholarships to MC and SK) and CNPq (National Council for Scientific and Technological Development: grant to the National Institute of Science and Technology for Pharmaceutical Innovation, INCT_if, and Universal Project to AP and SG), Brazil.
VL  - 8
IS  - art. 652137
SP  - 1
EP  - 14
PB  - Frontiers Media
CY  - Lausanne
ER  -