PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction
Migrino, Raymond Q.
Franco, Daniel A.
AffiliationUniv Arizona, Coll Med
MetadataShow full item record
PublisherTAYLOR & FRANCIS LTD
CitationDiana Guzman-Villanueva, Raymond Q. Migrino, Seth Truran, Nina Karamanova, Daniel A. Franco, Camelia Burciu, Subhadip Senapati, Dobrin Nedelkov, Parameswaran Hari & Volkmar Weissig (2017): PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction, Journal of Liposome Research, DOI: 10.1080/08982104.2016.1274756
JournalJOURNAL OF LIPOSOME RESEARCH
Rights© 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractLight chain (AL) amyloidosis is a disease associated with significant morbidity and mortality arising from multi-organ injury induced by amyloidogenic light chain proteins (LC). There is no available treatment to reverse the toxicity of LC. We previously showed that chaperone glycoprotein clusterin (CLU) and nanoliposomes (NL), separately, restore human microvascular endothelial function impaired by LC. In this work, we aim to prepare PEGylated-nanoliposomal clusterin (NL-CLU) formulations that could allow combined benefit against LC while potentially enabling efficient delivery to microvascular tissue, and test efficacy on human arteriole endothelial function. NL-CLU was prepared by a conjugation reaction between the carboxylated surface of NL and the primary amines of the CLU protein. NL were made of phosphatidylcholine (PC), cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (DSPE-PEG 2000 carboxylic acid) at 70:25:5mol%. The protective effect of NL-CLU was tested by measuring the dilation response to acetylcholine and papaverine in human adipose arterioles exposed to LC. LC treatment significantly reduced the dilation response to acetylcholine and papaverine; co-treatment of LC with PEGylated-nanoliposomal CLU or free CLU restored the dilator response. NL-CLU is a feasible and promising approach to reverse LC-induced endothelial damage.
NoteOpen access article.
VersionFinal published version
SponsorsCollege of Pharmacy-Glendale, Midwestern University