Rapid and continuous accumulation of nitric oxide-releasing liposomes in tumors to augment the enhanced permeability and retention (EPR) effect.

The modulation of blood flow to tumors is a prominent strategy for improving the tumor accumulation of nanomedicines, resulting from the enhanced permeability and retention (EPR) effect. We previously reported a promising EPR enhancer-a nitric oxide (NO) donor-containing liposome (NO-LP)-which showed enhanced accumulation in tumor tissue. Herein, we study NO-LP in greater detail to clarify its practical use as an EPR enhancer. NO-LP was found to have advantages as a NO donor, including the ability to maintain NO donation over long periods of time, and a constant rate of NO-release irrespective of the environmental pH. NO-LP showed rapid accumulation in tumor tissue after injection (1 h), and then accumulation was continuously enhanced until 48 h. Enhanced NO-LP accumulation was observed specifically in tumor, while the accumulation in other organs remained relatively unchanged. The results obtained show the promising features of NO-LP as an EPR enhancer.