(351f) ATP Delivery to Insulin Producing β Cells Using Peptide Targeted Liposomes

Islet cell transplantation is becoming a promising treatment option for patients with type 1 diabetes. However, stresses imposed during periods of ischemia, including isolation, culture, and after transplantation, reduce islet survival. The isolation process destroys the dense vascular network within the islet requiring diffusion to transport nutrients and oxygen to the cells within the islet. The period of low oxygen availability, known as hypoxia, during isolation limits the cell’s ability to produce adenosine triphosphate (ATP), the primary energy component within the cell, leading to loss of cell functions and eventually cell death.

In this work we demonstrate the synthesis, characterization, and application of targeted ATP containing liposomes (ATP-L) to insulin producing β cells. ATP is unable to cross the cell membrane but by encapsulating ATP within liposomes, intracellular delivery can be achieved. In our previous work, we have shown that functionalizing liposomes with the fibronectin-mimetic peptide, PR_b, increases binding and internalization of liposomes into pig islet cells that express the α₅β₁ integrin compared to conventional liposomes. Here we demonstrate the ability of the PR_b functionalized liposomes to deliver ATP to β cells. We show that delivery of exogenous ATP protects the cells from hypoxic mediated loss of cell function and death. This work highlights the promising role for PR_b targeted ATP-L in protecting β cells during periods of ischemia, potentially leading to increases in cell survival after both isolation and transplantation.