Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury

Amaraporn Wongrakpanich; Angie S Morris; Sean M Geary; Mei-ling A Joiner; Aliasger K Salem

doi:10.1016/j.ijpharm.2017.01.061

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Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury

Journal article

Peer reviewed

Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury

Amaraporn Wongrakpanich, Angie S Morris, Sean M Geary, Mei-ling A Joiner and Aliasger K Salem

International journal of pharmaceutics, Vol.520(1-2), pp.275-283

03/30/2017

DOI: 10.1016/j.ijpharm.2017.01.061

PMCID: PMC5401631

PMID: 28167264

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Abstract

[Display omitted] An excess of calcium (Ca2+) influx into mitochondria during mitochondrial re-energization is one of the causes of myocardial cell death during ischemic/reperfusion injury. This overload of Ca2+ triggers the mitochondrial permeability transition pore (mPTP) opening which leads to programmed cell death. During the ischemic/reperfusion stage, the activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) enzyme is responsible for Ca2+ influx. To reduce CaMKII-related cell death, sub-micron particles composed of poly(lactic-co-glycolic acid) (PLGA), loaded with a CaMKII inhibitor peptide were fabricated. The CaMKII inhibitor peptide-loaded (CIP) particles were coated with a mitochondria targeting moiety, triphenylphosphonium cation (TPP), which allowed the particles to accumulate and release the peptide inside mitochondria to inhibit CaMKII activity. The fluorescently labeled TPP-CIP was taken up by mitochondria and successfully reduced reactive oxygen species (ROS) caused by Isoprenaline (ISO) in a differentiated rat cardiomyocyte-like cell line. When cells were treated with TPP-CIP prior to ISO exposure, they maintained mitochondrial membrane potential. The TPP-CIP protected cells from ISO-induced ROS production and decreased mitochondrial membrane potential. Thus, TPP-CIP has the potential to be used in protection against ischemia/reperfusion injury.

Mitochondria targeting

PLGA

CaMKII

Details

Title: Subtitle: Surface-modified particles loaded with CaMKII inhibitor protect cardiac cells against mitochondrial injury
Creators: Amaraporn Wongrakpanich - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
Angie S Morris - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
Sean M Geary - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
Mei-ling A Joiner - Department of Molecular Physiology & Biophysics, Carver College of Medicine, University of Iowa, Iowa City, IA 52241, United States
Aliasger K Salem - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, United States
Resource Type: Journal article
Publication Details: International journal of pharmaceutics, Vol.520(1-2), pp.275-283
DOI: 10.1016/j.ijpharm.2017.01.061
PMID: 28167264
PMCID: PMC5401631
NLM abbreviation: Int J Pharm
ISSN: 0378-5173
eISSN: 1873-3476
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: P30 CA086862
Language: English
Date published: 03/30/2017
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Biology; Craniofacial Anomalies Research Center; Anesthesia; Dental Research; Chemical and Biochemical Engineering
Record Identifier: 9983985713802771

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