Delivery systems that are not eliminated by degradation,phagocytosis or glomerular filtration can leave the bloodstream bycrossing the endothelium to reach target tissues. This occurs mostreadily in tissues with discontinuous endothelia, such as in livertissues and many solid tumours90. Fenestrations in the liversinusoidal endothelium permit particles of 100–200nm in diameter toexit the bloodstream and gain access to hepatocytes and other livercells104,105. In some tumours, a combination of highly permeableendothelia and poor lymphatic drainage can lead to increasedaccumulation of circulating nanoparticles in malignant tissue — anoccurrence termed the enhanced permeation and retention effect
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