Liang, C.C.LiangBai, X.X.BaiQi, C.C.QiSun, Q.Q.SunHan, X.X.HanLan, T.T.LanZhang, H.H.ZhangZheng, X.X.ZhengLiang, R.R.LiangJiao, J.J.JiaoZheng, Z.Z.ZhengFang, J.J.FangLei, P.P.LeiWang, Y.Y.WangMöckel, D.D.MöckelMetselaar, J.M.J.M.MetselaarStorm, G.G.StormHennink, W.E.W.E.HenninkKiessling, F.F.KiesslingWei, H.H.WeiLammers, T.T.LammersShi, Y.Y.ShiWei, B.B.Wei2022-03-062022-03-062021https://publica.fraunhofer.de/handle/publica/26500310.1016/j.biomaterials.2020.120432Gastrointestinal (GI) cancers are among the most lethal malignancies. The treatment of advanced-stage GI cancer involves standard chemotherapeutic drugs, such as docetaxel, as well as targeted therapeutics and immunomodulatory agents, all of which are only moderately effective. We here show that P electron-stabilized polymeric micelles based on PEG-b-p(HPMAm-Bz) can be loaded highly efficiently with docetaxel (loading capacity up to 23 wt%) and potentiate chemotherapy responses in multiple advanced-stage GI cancer mouse models. Complete cures and full tumor regression were achieved upon intravenously administering micellar docetaxel in subcutaneous gastric cancer cell line-derived xenografts (CDX), as well as in CDX models with intraperitoneal and lung metastases. Nanoformulated docetaxel also outperformed conventional docetaxel in a patient-derived xenograft (PDX) model, doubling the extent of tumor growth inhibition. Furthermore, micellar docetaxel modulated the tumor immune microenvironment in CDX and PDX tumors, increasing the ratio between M1-and M2-like macrophages, and toxicologically, it was found to be very well-tolerated. These findings demonstrate that P electron-stabilized polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.en610journal article