Site-specific chelation therapy with EDTA-loaded albumin nanoparticles reverses arterial calcification in a rat model of chronic kidney disease

Scientific Reports
Saketh KaramchedNaren Vyavahare

Abstract

Medial arterial calcification (MAC) is a common outcome in diabetes and chronic kidney disease (CKD). It occurs as linear mineral deposits along the degraded elastin lamellae and is responsible for increased aortic stiffness and subsequent cardiovascular events. Current treatments for calcification, particularly in CKD, are predominantly focused on regulating the mineral disturbance and other risk factors. Ethylene diamine tetraacetic acid (EDTA), a chelating agent, can resorb mineral deposits, but the systemic delivery of EDTA may cause side effects such as hypocalcemia and bone resorption. We have developed elastin antibody conjugated albumin nanoparticles that target only degraded elastin in vasculature while sparing healthy tissues. In this study, we tested a targeted nanoparticle-based EDTA chelation therapy to reverse CKD-associated MAC. Renal failure was induced in Sprague-Dawley rats by a high adenine diet supplemented by high P and Ca for 28 days that led to MAC. Intravenous delivery of DiR dye-loaded nanoparticles confirmed targeting to vascular degraded elastin and calcification sites within 24 hours. Next, EDTA-loaded albumin nanoparticles conjugated with an anti-elastin antibody were intravenously injected twice a ...Continue Reading

References

May 4, 1999·Clinical and Diagnostic Laboratory Immunology·R GendronD Mayrand
Aug 2, 2001·Herz·D Proudfoot, C M Shanahan
Nov 1, 1953·Proceedings of the Society for Experimental Biology and Medicine·J F HOLLANDA SAHAGIAN-EDWARDS
Mar 11, 2008·Respiratory Medicine·Gillian E LowreySimon R Johnson
Aug 5, 2008·Molecular Pharmaceutics·Frank AlexisOmid C Farokhzad
Sep 27, 2008·Kidney International·Andreas PaschStefan Farese
Jan 9, 2009·Kidney International·Koba A LomashviliW Charles O'Neill
Jan 16, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ellen NevenVeerle Persy
Jan 16, 2009·Kidney International·Cecilia M Giachelli
May 30, 2009·Journal of the American Society of Nephrology : JASN·Masahide MizobuchiEduardo Slatopolsky
Apr 24, 2010·American Journal of Nephrology·Navid ShobeiriRachel M Holden
Sep 24, 2010·Kidney International·W Charles O'Neill, Koba A Lomashvili
Jan 22, 2011·Circulation Research·Ellen Neven, Patrick C D'Haese
Sep 3, 2011·Circulation Research·Catherine M ShanahanCecilia M Giachelli
Oct 12, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shunsuke YamadaTakanari Kitazono
Dec 17, 2011·American Heart Journal·Gervasio A LamasKerry L Lee
Nov 1, 2012·British Journal of Clinical Pharmacology·Oscar LeonardDavid Goldsmith
Mar 28, 2013·JAMA : the Journal of the American Medical Association·Gervasio A LamasUNKNOWN TACT Investigators
May 31, 2013·BMC Nephrology·Ting JiaTobias E Larsson
Jun 5, 2013·Journal of Pharmacological and Toxicological Methods·Vishal DiwanLindsay Brown
Jun 22, 2013·Clinical and Experimental Hypertension : CHE·Alexandra Gauthier-BastienMohsen Agharazii
Aug 22, 2013·Calcified Tissue International·Yang LeiNaren Vyavahare
Jan 24, 2014·Nature Materials·Ralph WeisslederMikael J Pittet
Feb 26, 2014·Nanomedicine : Nanotechnology, Biology, and Medicine·Aditi SinhaNaren Vyavahare
Oct 7, 2014·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yang LeiNaren Vyavahare
Aug 20, 2016·Journal of Cardiovascular Translational Research·Nasim NosoudiNaren Vyavahare
Jan 27, 2017·Circulation·Emelia J BenjaminUNKNOWN American Heart Association Statistics Committee and Stroke Statistics Subcommittee

❮ Previous
Next ❯

Citations

Jun 18, 2020·International Journal of Nanomedicine·Rajasekharreddy PalaSurya M Nauli
Jun 20, 2020·British Journal of Pharmacology·Joan PerellóCarolina Salcedo
Apr 18, 2019·International Journal of Molecular Sciences·Stefania RaimondoRiccardo Alessandro
Nov 11, 2020·Pharmaceutics·Artur Y PrilepskiiVladimir V Vinogradov
Feb 24, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Manuel Alfredo PodestàMario Cozzolino
Jul 31, 2021·Environmental Science and Pollution Research International·Anil KumarDeepak Pant

❮ Previous
Next ❯

Methods Mentioned

BETA
Fluorescence

Software Mentioned

Skyscan Nrecon

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.