Development of Triiodothyronine Polymeric Nanoparticles for Targeted Delivery in the Cardioprotection against Ischemic Insult
Authors: Shaker A Mousa
Thangirala Sudha
Brian Weil
Kazutoshi Fujioka
Ozlem Ozen Karakus
Peter C Taylor Dickinson
Taher A Salaheldin
Noureldien H E Darwish
Journal: Biomedicines (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Nano-T3; cardiac arrest; ischemia; phosphocreatine; resuscitation
Affiliations: The Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA., Pro-Al Medico Technologies Inc., Suffern, NY 10901, USA., Departments of Physiology & Biophysics, School of Medicine & Biomedical Sciences, University at Buffalo, Buffalo, NY 14203, USA.

Abstract:  Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate T3 delivery and restrict its nuclear translocation. Modified T3 and PLGA-T3 was characterized with 1H-NMR. The protective role of synthesized phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults was investigated. The results showed that PLGA-T3/PCr NPs represent a potentially new therapeutic agent for the control of tissue damage in cardiac ischemia and resuscitation. 

Retracted: No

PubPeer comments:
 Two images in Figure 6A appear to overlap, after 180-degree rotation. Note: the last author appears to be Editor-in-Chief of this journal. ***  ***  , 
 #1 We appreciate your kind replay Regarding to image 6A; we check the images, and we didnu2019t find any overlap between the images as well as throughout our image s library. Also, regarding the 2nd comments (Note: the last author appears to be Editor-in-Chief of this journal); our Manuscript has been handled by independent editors excluding Dr. Mousa from the whole process. The Manuscript has been passed through 2 different revision cycles with experts. Actually, in the 1st revision; the manuscript has been rejected and in the second revision we did a lot of work to improve the MS (answering more than 30 comments) Thank you again. , 
 #2 Dear Dr. Mousa, I fail to understand how you could possibly deny the overlap between the two images indicated in comment #1. This is absolutely evident to anyone whose eyesight works normally. , 
 #2  Regarding to image 6A; we check the images, and we didnu2019t find any overlap between the images as well as throughout our image s library. Don t forget to rotate one of the panels through 180-deg. , 
 We did submit corrected Figure panels to the Journal Thanks for your comments , 
 We provided the corrected Figure the Journal along with the explaianations , 
 #6 It would be appreciated if you could also provide the images here, as the journal, and initially, you yourself, were unable to identify the issue. As you appear to be Editor-in-Chief of this journal, it would be nice to have an independent party review the original data. External sites for larger files can be linked here. Some options: http: figshare.com http: Imgur.com https: www.google.com drive , 
 Received: 8 June 2022 Accepted: 8 June 2022 Published: 13 June 2022 In the published manuscript [1] in the Results section, in the subsection titled 3.5. Cardioprotective Effects of T3 and PLGA-T3 PCr NPs under Hypoxia, in Figure 6A there was an unintentional mistake of an overlap in Figures under different treatment conditions while taking photographs labeling at a lower magnification. Experiment was repeated and photographs were taken under higher magnification for improved image quality. The scientific conclusion was unaffected and there is no change in the legend of the figure. The published figure is replaced with the new Figure 6A.  , 
 #8 The experiments were apparently repeated, although there doesnu2019t seem to be an explanation for why. Was the original data no longer available? That seems to contradict your comment in January that you had reviewed the u201cimage library.u201d See #2. If the original data is missing, why does there appear to be no change in the quantification shown in Figure 6? Wouldnu2019t those graphs need to be updated to reflect the new results? *** Original Figure 6.  , 
 Biomedicines Corrected Figure 6A: Expression of troponin T in neonatal cardiomyocytes under hypoxic condition where Immunostaining by anti-troponin T-PE (confocal microscopy) as shown in the representative image (A). Bar graph under A images showed average Troponin T fluorescence intensity cell (%) + SEM, n = 3 where the average data were consistent as reported in the original manuscript and the corrected one. Furthermore, bar graph quantitation of troponin T in neonatal cardiomyocyte and in medium using flow cytometry and ELISA (B) supported the finding documented by confocal imaging. These results suggest that PLGA-T3 NPs and PLGA-T3 NPs PCr inhibit the damaging effect of hypoxia on cardiomyocytes as shown in Figure 6 A and B . , 
 Dr. Mousa, could you also provide a clarification on the funding and conflict of interest disclosures in this paper?  While the Funding section says there was no external funding, the Acknowledgements section says that funding was received from Pro-Al Medico Technologies Inc, as well as the author s institution. That seems contradictory. Also, searching for some information on Pro-Al Medico Technologies, it seems as if the CEO is was Leo Rubin who is a co-inventor with Dr. Mousa on one or more patents. Could you provide details about any relationship between yourself, Dr. Rubin, Pro-Al Medico, and patents that might be related to this research? Thank you. ,