@article{oai:hama-med.repo.nii.ac.jp:00003771, author = {Shimizu, Kosuke and Takeuchi, Yoshihito and Otsuka, Kazuma and Mori, Tomoya and Narita, Yudai and Takasugi, Shohei and Magata, Yasuhiro and Matsumura, Yasuhiro and Oku, Naoto}, journal = {Journal of Controlled Release}, month = {Jul}, note = {<参照>出版社サイト:https://doi.org/10.1016/j.jconrel.2020.04.043, Tissue factor (TF), which is well known as a trigger molecule of extrinsic coagulation, is found in not only tumor cells but also in stromal cells in tumor tissues. Thus, TF is a candidate molecule to potentially enable targeting of both tumor cells and stromal cells for anti-cancer drug delivery. Herein, we prepared liposomes conjugated with the Fab’ fragment of anti-TF antibody (TF Ab- Lip) and evaluated the capability for drug delivery to stroma-rich tumors for realizing a whole tumor tissue-targetable strategy. When the targetability of TF Ab-Lip to TF-expressing KLN205 squamous tumor cells and NIH3T3 fibroblast cells were examined, TF Ab-Lip was significantly taken up into both cells compared with non-targeted liposomes. Corresponding to this result, doxorubicin-encapsulated TF Ab-Lip (TF Ab-LipDOX) showed potent cytotoxicity against KLN205 cells. In vivo experiments using KLN205 solid tumor-bearing mice indicated that TF Ab-Lip became highly accumulated and distributed widely in not only the tumor cell region but also in the stromal one in the tumor. Treatment with TF Ab-LipDOX significantly suppressed the growth of KLN205 solid tumors. Furthermore, TF Ab-Lip targetable both mouse and human TF (mhTF Ab-Lip) became distributed throughout stroma-rich human pancreatic BxPC3 tumors and the treatment of the BxPC3 tumor-bearing mice with mhTF Ab-LipDOX showed highest tumor suppressive effect. These data suggest that TF Ab-Lip could achieve effective accumulation for stroma-rich tumor treatment.}, pages = {519--529}, title = {Development of tissue factor-targeted liposomes for effective drug delivery to stroma-rich tumors}, volume = {323}, year = {2020} }