Fig. 7.

Vessel normalization improves NP delivery. a Proposed role of vessel normalization in the response of tumors to anti-angiogenic therapy. a Normal vessel structure. b Tumor vasculature structure. Tumor vessel is structurally and functionally abnormal, providing resistance to the delivery of small molecules and NP. c Dynamic vascular normalization induced by VEGFR blockade. (Reproduced from Carmeliet et al. 2011, copyright of Nature publishing group) b Effects of vascular normalization on NP delivery and therapy in 4T1 and E0771 tumors. a NP penetration versus particle size in orthotopic 4T1 mammary tumors in response to normalizing therapy with DC101. NP concentrations (denoted by pseudocolor) are relative to initial intravascular levels, with vessels shown in black. b Penetration rates (transvascular flux) for NP in E0771 tumors in mice treated with DC 101, a and b indicates that normalization improves 12 nm NP penetration while not affecting 125 nm penetration. Scale bar, 100 μm. c Cytotoxic nanomedicine effectiveness by vascular normalization. Quantification of tumor growth rates based on the time to reach double the initial volume. Abraxane (10 nm) and Doxil (100 nm) monotherapy induce growth delays versus the control treatment. Normalization with DC101 enhances the effectiveness of the 10 nm Abraxane, but does not affect that of the 100 nm Doxil (Detailed description refers to the original manuscript, Chauhan et al. 2012, copyright of Nature publishing group)