Tumors capillary fenestrations

Passive targeting occurs due to extravasation of the nanoparticles at the diseased site where the microvasculature is leaky. Passive delivery refers to nanoparticle s transport through leaky tumor capillary fenestrations into the tumor interstitium and cells by passive diffusion or convection (Haley and Frenkel 2008). What is important to understand, passive targeting proceeds based on natural developed... 

There is an increased blood flow in brain tumors (ref. 589), and the blood-brain barrier is leaky in and around 9L tumors because the blood vessels associated with these (ref. 568), and other (ref. 565-567), tumors are fenestrated. This well-known leakiness of tumor capillaries, which in the case of brain tumors includes breaches in the blood-brain barrier (ref. 566,568 cf. Section 12.2), would allow extravasation of small particulate matter (cf. ref. 590-594) or LCM. Once in the tumor area, LCM remain there because of an affinity for tumor cell surface components (cf. ref. 531 see also Chapter 14). At least 4 different types of experimental tumors in rats (C6 glioma, 9L gliosarcoma, Novikoff hepatoma, and Walker-256 carcinosarcoma), as well as several spontaneous tumors in dogs (ref. 570), do interact with LCM in a preferential manner (cf. Chapters 12 and 13), suggesting that LCM affinity may be for tumor cells in general (ref. 531). 

The effectiveness of cisplatin depends on its ability to penetrate target tissue. Therefore, we need to estimate its penetration depth from a distributed model such as that represented by Equation 9.1. However, this is difficult to do with ovarian tumors because the permeabilities and reaction rates are not available. Hence, a first estimate is made for penetration of normal peritoneal cavity tissues by ethylenediamine-tetraacetic acid (EDTA), a molecule of molecular weight similar to that of cisplatin. The steady-state concentration profiles of EDTA should resemble those of cisplatin in normal peritoneal tissues because both compounds are cleared primarily by permeation through the fenestrated capillaries in these tissues, and the small molecular weight-related differences in P s and D should cancel out in Equations 9.5 and 9.5T By first focusing on EDTA, experimental data also become available for assessing the ability of the distributed model to account for the observed spatial dependent of concentration. 

Attracts CLA+ T cells and directs them into the skin Attracts lymphocyte subsets during inflammation facilitates certain immune response Stimulates proliferation of epidermal and epithelial cells inhibits gastric secretion involves in wound healing Induces proliferation and migration fenestration in capillary endothelial cells Inhibits endothelial cell proliferation, vasculogenesis, neovessel formation inhibits angiogenesis of vascular beds suppresses tumor growth induces apoptosis and myeloperoxidase activity from neutrophils... 

Fig. 3 Structures of (a) normal and (b) tumor tissue, and the in/out transport from capillaries of various substances. Although large macromolecules cannot penetrate normal tissue, and small molecules and proteins are cleared by lymphatics, blood vessels in tumors present large fenestrations that cause macromolecules to permeate extensively into the tumor tissue. Moreover, slow venous return and poor lymphatic clearance retain macromolecules in the tumor. These phenomena are called the enhanced permeability and retention (EPR) effect [18]. Reprinted with permission from Reference [18]...

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