Fig. 5.

The influence of collagen crosslinking and alignment on NP distribution. a The architecture of the collagen scaffold changes from early thin relaxed structures (curly fibrils) to thick, linearized, and highly aligned structures during malignancy development. (Reproduced from Egeblad et al. 2010, copyright of Elsevier) b Typical fiber structure established in vitro using a mathematical model. c Diffusion anisotropy as a function of the particle radius over the fiber radius for the fiber structures employed in the study. Results indicate that the more aligned one has a more strict distribution direction. (b, c reproduced from Stylianopoulos. 2010, copyright of Elsevier. Detailed description refers to the original manuscript.) d Immunostaining of collagen I in the two in vivo tumor models. Mu89 has highly aligned fibril structure that separate tumors into different compartments, while HSTS26T has dense collagen but less fibril structure. Losartan treatment can decrease the collagen content in both tumors. e A scheme hypothesis for losartan treatment in the two tumor models with a different collagen pattern. It indicates that the aligned and highly cross-linked tumors have limited NP perfusion after Losartan treatment, while the less fibril-like tumors have more scattered NP perfusion after Losartan treatment (d, e reproduced from Diop-Frimpong et al. 2011, copyright of National Academy of Sciences of the United States of America)