# Enhancement of EPR Effect for Passive Tumor Targeting: Current Status and Future Perspectives
## 3 Morphological Characteristics of the Vascular Network
### Functional Characteristics of the Tumor Vascular System
#### 3.4.5 Vascular Mediators Related to the EPR Phenomenon
The inhibition of one factor can significantly reduce the EPR effect but not eliminate it completely. Conversely, the activation of one factor can trigger the activation of many other steps, rapidly leading to an intense EPR effect [8]. Table 2 summarizes all the information related to the morphological characteristics of the vascular network as mentioned in Section 3. \begin{table}
\begin{tabular}{c c c} \hline \hline
**Section** & **Details** & **References** \\ \hline \multirow{2}{*}{Vascular Network Morphology} & Tumor vasculature is disorganized with structural and functional abnormalities due to overexpression of angiogenic factors. & [72; 73] \\ \hline \multirow{2}{*}{Vascular Network Hypervascularity} & Tumors exhibit hypervascularity with regions of & \\  & increased microvascular density (hot spots), & [8; 84; 85] \\  & increasing the likelihood of metastasis. & \\ \hline \multirow{2}{*}{Intravascular Environment} & Endothelial cells (ECs) are poorly connected in tumors & \\  & and may form multilayered structures with irregular & [74; 75; 79; 80; 81] \\  & basement membranes. & \\ \hline \multirow{2}{*}{Tumor Vascularity vs. Normal Vascularity} & Tumor vessels are more variable in size and structure, & \\  & larger than normal, and show branching and & [74; 76; 77; 78] \\  & convoluted pathways. & \\ \hline \multirow{2}{*}{Types of Blood Vessels in Tumors} & Tumors include arteries, arterioles, capillaries, & \\  & venules, and veins, with varying structures based on & [74; 75; 76; 77; 78; 79; 80; 81] \\  & tissue function. & \\ \hline \multirow{2}{*}{Factors Influencing Vascularization} & Cancer and stromal cells secrete angiogenic and & \\  & growth factors, which stimulate abnormal blood & [74; 75] \\  & vessel formation. & \\ \hline \multirow{2}{*}{Vascular Smooth Muscle and Pericytes} & Vascular smooth muscle cells support arteries, and & \\  & pericytes stabilize smaller vessels, contributing to & [81; 88] \\  & endothelial cell (EC) proliferation. & \\ \hline \multirow{2}{*}{Blood Flow} & Tumor blood flow follows a similar pattern as in & \\  & normal tissue, with greater structural abnormalities in & [74] \\  & blood vessels. & \\ \hline \multirow{2}{*}{Irregular Blood Flow} & Increased microvascular pressures, vessel & \\  & abnormalities, and blood flow resistance contribute to & \\  & tumor hypoxia and reduced perfusion despite high & [85; 100; 102; 104] \\  & vascular density. & \\ \hline \multirow{2}{*}{Blood Flow Regions in Tumors} & Vascular regions in tumors: necrotic (no blood flow), & \\  & semi-necrotic (some blood flow), stabilized & [104] \\  & microcirculation, and advanced fronts. & \\ \hline \multirow{2}{*}{Tumor Vascular System Functional Features} & Unique features like angiogenesis, hyperangiogenesis, & \\  & irregular blood flow, vascular permeability, and & \\  & abnormal lymphatic drainage describe the EPR & [72; 85] \\  & phenomenon. & \\ \hline \multirow{2}{*}{Angiogenesis} & Essential for tumor growth, triggered by hypoxia, & \\  & enables migration, nutrient supply, and waste & \\  & disposal. Process involves sprouting, de novo & \\  & angiogenesis, and division of parent vessels. & \\ \hline \multirow{2}{*}{Angiogenesis Mechanism} & A 4-stage process involving cytokine release, & \\  & endothelial cell proliferation, and pericyte fixation. & \\  & Endothelial cells form filopodia, proliferate, and & [77; 92; 93; 96] \\  & recruit pericytes. & \\ \hline \multirow{2}{*}{Angiogenesis Regulation} & Balance between pro-angiogenic and anti-angiogenic & \\  & factors. Overexpression of pro-angiogenic factors & [87; 94; 95] \\  & leads to cancer growth. & \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Summary of all the information about the morphological characteristics of the vascular network.