PLGA from PolySciTech used in development of cardiovascular targeting nanoparticle for heart therapies

 

Notch, a specific signaling protein, is essential for proper development of the heart as this regulates signals between the endocardium and myocardium for chamber development. The ability to deliver genetic factors to correct issues with this signal formation can be used to aid in specific cardiovascular disease or formation issues. Recently, researchers at University of Texas at Arlington, University of North Texas, and University of California, Irvine used PLGA (cat# AP154) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with Notch plasmid to test the delivery of this gene to cells. They also tested the particles for any prevelant environmental danger which, owing to the biocompatible and biodegradable nature of PLGA, were minimal. Read more: Messerschmidt, V., Uday Chintapula, Fabrizio Bonetesta, Samantha Laboy-Segarra, Amir Naderi, K. Nguyen, Hung Cao, Edward Mager, and Juhyun Lee. "In vivo Evaluation of Non-viral NICD Plasmid-Loaded PLGA Nanoparticles in Developing Zebrafish to Improve Cardiac Functions." Frontiers in physiology 13 (2022). https://europepmc.org/articles/pmc8906778/bin/data_sheet_1.pdf

“Abstract: In the era of the advanced nanomaterials, use of nanoparticles has been highlighted in biomedical research. However, the demonstration of DNA plasmid delivery with nanoparticles for in vivo gene delivery experiments must be carefully tested due to many possible issues, including toxicity. The purpose of the current study was to deliver a Notch Intracellular Domain (NICD)-encoded plasmid via poly(lactic-co-glycolic acid) (PLGA) nanoparticles and to investigate the toxic environmental side effects for an in vivo experiment. In addition, we demonstrated the target delivery to the endothelium, including the endocardial layer, which is challenging to manipulate gene expression for cardiac functions due to the beating heart and rapid blood pumping. For this study, we used a zebrafish animal model and exposed it to nanoparticles at varying concentrations to observe for specific malformations over time for toxic effects of PLGA nanoparticles as a delivery vehicle. Our nanoparticles caused significantly less malformations than the positive control, ZnO nanoparticles. Additionally, the NICD plasmid was successfully delivered by PLGA nanoparticles and significantly increased Notch signaling related genes. Furthermore, our image based deep-learning analysis approach evaluated that the antibody conjugated nanoparticles were successfully bound to the endocardium to overexpress Notch related genes and improve cardiac function such as ejection fraction, fractional shortening, and cardiac output. This research demonstrates that PLGA nanoparticle-mediated target delivery to upregulate Notch related genes which can be a potential therapeutic approach with minimum toxic effects. Keywords: PLGA nanoparticles, toxicity, non-viral transfection, zebrafish, gene delivery, Notch signaling”