RT Journal Article
SR Electronic
T1 Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.16.440241
DO 10.1101/2021.04.16.440241
A1 Victoria L. Messerschmidt
A1 Aneetta E. Kuriakose
A1 Uday Chintapula
A1 Samantha Laboy
A1 Thuy Thi Dang Truong
A1 LeNaiya A. Kydd
A1 Justyn Jaworski
A1 Kytai T. Nguyen
A1 Juhyun Lee
YR 2021
UL http://biorxiv.org/content/early/2021/04/18/2021.04.16.440241.abstract
AB Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domain-containing plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.Competing Interest StatementThe authors have declared no competing interest.