The use of antibody modified liposomes loaded with AMO-1 to deliver oligonucleotides to ischemic myocardium for arrhythmia therapy

Biomaterials. 2014 Apr;35(11):3697-707. doi: 10.1016/j.biomaterials.2013.12.099. Epub 2014 Jan 24.


MicroRNA-1 (miR-1) has been found in cardiac and skeletal tissues. It is overexpressed in ischemic cardiac tissues. Down-regulation of miR-1 could relieve arrhythmogenesis by the anti-miR-1 antisense oligonucleotides (AMO-1). To increase the therapeutic efficiency and inhibit off-target effects of AMO-1, here we explored anti-cardiac troponin I (cTnI) antibody modified liposomes loading with AMO-1 (cT-A-LIP) to deliver the oligonucleotides to ischemic myocardium tissues. Liposomal cytotoxicity was assessed by MTT assay. The targeting abilities to foci were evaluated by in vivo imaging. The uptake and bio-distribution in vitro were observed by live cell station and flow cytometry, respectively. The anti-arrhythmic effects of cT-A-LIP in vivo were evaluated by electrocardiograms (ECG), immunohistochemistry, real-time PCR and patch-clamp recording. Immunohistochemistry showed that cTnI expression had a peak at the third day after myocardial infarction (MI). After cT-LIP administration via tail vein, accumulation of fluorescent trackers in the ischemic foci was significantly increased more than that of LIP. In addition, after cT-A-LIP administration, the ischemic arrhythmias were recovered and ST segment in ECG was elevated nearly back to normal. Compared with MI group, miR-1 expression was significantly down-regulated while Kir2.1 and CX43 protein expression were increased. Patch-clamp recordings showed that cT-A-LIP as well as AMO-1 incubation increased K(+) current density in guinea pigs ventricular cardiomyocytes acting on repolarized membrane potential. In conclusion, the cT-A-LIP not only delivered AMO-1 to ischemic myocardium in MI rats, but validated AMO-1 on relieving ischemic arrhythmia by silencing of miR-1 in ischemic myocardium and restoring the depolarized resting membrane potential (RMP) in MI rats.

Keywords: Anti-cTnI antibody; Antisense oligonucleotide; In vivo imaging; Ischemic arrhythmias; Liposomes; MicroRNA-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / metabolism*
  • Arrhythmias, Cardiac / complications*
  • Arrhythmias, Cardiac / diagnostic imaging
  • Arrhythmias, Cardiac / pathology
  • Arrhythmias, Cardiac / therapy*
  • Cell Survival / drug effects
  • Flow Cytometry
  • Liposomes / chemistry*
  • Liposomes / ultrastructure
  • MicroRNAs / metabolism
  • Myocardial Ischemia / complications*
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / pathology
  • Myocardial Ischemia / therapy*
  • Myocardium / pathology
  • Oligonucleotides, Antisense / pharmacology*
  • Particle Size
  • Rats
  • Rats, Wistar
  • Static Electricity
  • Time Factors
  • Time-Lapse Imaging
  • Troponin I / metabolism
  • Ultrasonography


  • Antibodies
  • Liposomes
  • MIRN1 microRNA, rat
  • MicroRNAs
  • Oligonucleotides, Antisense
  • Troponin I