@article{74f35809395c4efe937fc779c0d8b974,
title = "Π electron-stabilized polymeric micelles potentiate docetaxel therapy in advanced-stage gastrointestinal cancer",
abstract = "Gastrointestinal (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 Π 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 Π electron-stabilized polymeric micelles loaded with docetaxel hold significant potential for the treatment of advanced-stage GI cancers.",
keywords = "Gastrointestinal cancer, Nanomedicine, Polymeric micelles, Taxane therapy, Tumor microenvironment, Tumor targeting",
author = "Chenghua Liang and Xiangyang Bai and Cuiling Qi and Qingxue Sun and Xiaoyan Han and Tianyun Lan and Haibo Zhang and Xiaoming Zheng and Rongpu Liang and Ju Jiao and Zongheng Zheng and Jiafeng Fang and Purun Lei and Yan Wang and Diana M{\"o}ckel and Metselaar, {Josbert M.} and Gert Storm and Hennink, {Wim E.} and Fabian Kiessling and Hongbo Wei and Twan Lammers and Yang Shi and Bo Wei",
note = "Funding Information: This work was supported by grants from Science and Technology Planning Project of Guangdong Province ( 2017B020227009 and 2017A010103009 ), by Fundamental Research Funds for the Central Universities ( 16ykjc23 ), by the National Natural Science Foundation of China ( 81472825 and 81773095 ), by the Outstanding Young Talents Support Program of the Third Affiliated Hospital of Sun Yat-sen University , by the China Scholarship Council ( CSC ), by the European Research Council (ERC: Consolidator Grant Meta-Targeting ( 864121 ) and Proof-of-Concept Grant PIcelles ( 813086 )), by German Research Foundation ( DFG : GRK/RTG 2375: Tumor-targeted Drug Delivery (project number 331065168 )), and by the Aachen Interdisciplinary Center for Clinical Research (IZKF; Project O3-2). Funding Information: This work was supported by grants from Science and Technology Planning Project of Guangdong Province (2017B020227009 and 2017A010103009), by Fundamental Research Funds for the Central Universities (16ykjc23), by the National Natural Science Foundation of China (81472825 and 81773095), by the Outstanding Young Talents Support Program of the Third Affiliated Hospital of Sun Yat-sen University, by the China Scholarship Council (CSC), by the European Research Council (ERC: Consolidator Grant Meta-Targeting (864121) and Proof-of-Concept Grant PIcelles (813086)), by German Research Foundation (DFG: GRK/RTG 2375: Tumor-targeted Drug Delivery (project number 331065168)), and by the Aachen Interdisciplinary Center for Clinical Research (IZKF; Project O3-2). Publisher Copyright: {\textcopyright} 2020 Elsevier Ltd",
year = "2021",
month = jan,
doi = "10.1016/j.biomaterials.2020.120432",
language = "English",
volume = "266",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",
}