One clinical study reported that most (>98%) of the drug circulating in the blood stream remains in encapsulated in liposomes [61] , suggesting that little of the liposomal drugs will be leaked to the circulation system during its journey to the tumor tissues. The hyperpermeability of tumor vasculature is a key factor for the success of liposome-delivered chemotherapy agents. The "leakiness" of the angiogenic tumor vasculature is estimated to have an average pore size of 100-600 nm [66] . These pores are significantly larger than the gap junction found in normal endothelium, which are typically <6 nm wide [67] . Liposomes with diameters of approximately 65-75 nm [13, 14, 50] are small enough to passively infiltrate tumor endothelium but large enough to be excluded from normal endothelium. Hence, they selectively extravasate into the tumor interstitial space. In the tissue of solid tumors, vasculature becomes so permeable that particulate liposomes can extravasate and localize in the tissue interstitial space [6, 10] . In addition, tumor tissues frequently lack effective lymphatic drainage [3] , which means that the liposomes can be retained longer. Together, these factors increase the Journal of Oncology 5 accumulation of the drug within the tumor, which has been referred to as the "enhanced permeability and retention (EPR) effect" by Maeda et al. [68, 69] . EPR-mediated passive tumor targeting by liposomes can increase the concentration of drugs in solid tumors by as much as ten times, compared to free drugs [70] .