Nanoghosts – a drug delivery platform for inflamed cardiac tissue

Cardiac injuries, like heart attacks, drive the secondary pathology with advanced heart failure. In this process, inflammation is a primary component of accelerated cardiovascular disease and subsequent fatal events¹. Literature shows that targeting the IGF1-PI3K pathway can improve the function of the failing rodent heart. Further, the IGF1-PI3K pathway is highly conserved across species. However, despite strong evidence for targeting this pathway in the human failing heart, there are challenges targeting this pathway in the failing heart due to ubiquitous expression of the pathway and the potential for adverse consequences in other tissues².
Our laboratory has developed unique membrane-based nano-vesicles produced from the plasma membranes of mesenchymal stem cells (MSCs), termed Nanoghosts (NGs). While their production these nanoparticles preserve the original features of MSCs. As part of their natural role in wound healing and immunomodulation, MSCs are known to home in on diverse sites of inflammation and injuries.
We hypothesize that NGs would have become a perspective targeting delivery platform for cardiac diseases. Therefore, this research aims to optimize the NGs delivery platform to target the inflamed cardiac tissue and to deliver the protein of interest – IGF-1³.

References:
1. Pullen AB, Jadapalli JK, Rhourri-Frih B, Halade GV. Re-evaluating the causes and consequences of non-resolving inflammation in chronic cardiovascular disease. Heart Fail Rev. 2020
2. McMullen JR, Amirahmadi F, Woodcock EA, Schinke-Braun M, Bouwman RD, Hewitt KA, Mollica JP, Zhang L, Zhang Y, Shioi T, Buerger A, Izumo S, Jay PY, Jennings GL. Protective effects of exercise and phosphoinositide 3-kinase(p110alpha) signaling in dilated and hypertrophic cardiomyopathy. Proc. Natl. Acad. Sci. U. S. A.2007;104:612-617
3. L. Kaneti, T. Bronshtein, N. Malkah Dayan, I. Kovregina, N. Letko Khait, Y. Lupu-Haber, M. Fliman, B.W. Schoen, G. Kaneti, M. Machluf, Nanoghosts as a Novel Natural Nonviral Gene Delivery Platform Safely Targeting Multiple Cancers, Nano Lett. 16 (2016) 1574–1582. doi:10.1021/acs.nanolett.5b04237.