Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

PEGylated-nanoliposomal clusterin for amyloidogenic light chain-induced endothelial dysfunction. J Liposome Res 2018 Jun;28(2):97-105 PMID: 28103719 PMCID: PMC5591079

Pubmed ID

28103719

Abstract

Light 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 70:25:5 mol%. 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.

Author List

Guzman-Villanueva D, Migrino RQ, Truran S, Karamanova N, Franco DA, Burciu C, Senapati S, Nedelkov D, Hari P, Weissig V

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




jenkins-FCD Prod-300 626508253d14e4184314fb9f66322a03a5906796