PMID- 34859546 OWN - NLM STAT- MEDLINE DCOM- 20220211 LR - 20220216 IS - 1349-7006 (Electronic) IS - 1347-9032 (Print) IS - 1347-9032 (Linking) VI - 113 IP - 2 DP - 2022 Feb TI - Paclitaxel-based supramolecular hydrogel loaded with mifepristone for the inhibition of breast cancer metastasis. PG - 733-743 LID - 10.1111/cas.15230 [doi] AB - Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel could be an effective strategy for inhibiting breast cancer metastasis. However, their inherent defects, in terms of short blood circulation half-life and lack of tumor targeting, not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by a nanodelivery system, and explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The antimetastatic effect was evaluated in vitro and in vivo and its mechanism was also explored by western blot assay. The resultant PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake properties and stimulated drug release in the tumor micro-acidic environment. The PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. The PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and MMPs. Taken together, PM-nano showed superior antimetastatic effects against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for limiting metastasis. CI - (c) 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. FAU - Zhao, Cui-Cui AU - Zhao CC AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Zhang, Chuan-Gui AU - Zhang CG AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Sun, Xuan AU - Sun X AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Guo, Qingxiang AU - Guo Q AD - Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, and Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Liu, Jinjian AU - Liu J AD - Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, and Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Liu, Yan AU - Liu Y AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Hao, Ya-Nan AU - Hao YN AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Feng, Guowei AU - Feng G AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Yang, Lijun AU - Yang L AD - Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, and Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. FAU - Liu, Hong AU - Liu H AD - Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. FAU - Liu, Jianfeng AU - Liu J AUID- ORCID: 0000-0003-0541-5072 AD - Key Laboratory of Radiopharmacokinetics for Innovative Drugs, Chinese Academy of Medical Sciences, and Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China. LA - eng GR - 18JCJQJC47300/National Science Fund for Distinguished Young Scholars of Tianjin/ GR - 81701840/National Natural Science Foundation of China/ GR - 2016-I2M-3-022/CAMS Innovation Fund for Medical Sciences/ GR - 19ZXDBSY00090/Major Science and Technology Project for prevention and Treatment of major diseases in Tianjin/ GR - 2018PT35031/Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences/ PT - Journal Article DEP - 20211218 PL - England TA - Cancer Sci JT - Cancer science JID - 101168776 RN - 0 (Antineoplastic Agents) RN - 0 (Drug Carriers) RN - 0 (Hydrogels) RN - 320T6RNW1F (Mifepristone) RN - P88XT4IS4D (Paclitaxel) SB - IM MH - Animals MH - Antineoplastic Agents/chemistry/pharmacology/*therapeutic use MH - Biological Availability MH - Breast Neoplasms/*drug therapy/pathology MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Drug Carriers/chemistry/pharmacology/therapeutic use MH - Drug Liberation MH - Female MH - Humans MH - Hydrogels/chemistry/pharmacology/*therapeutic use MH - Mice MH - Mifepristone/chemistry/pharmacology/*therapeutic use MH - Nanostructures/therapeutic use MH - Paclitaxel/chemistry/pharmacology/*therapeutic use MH - Tumor Burden/drug effects MH - Xenograft Model Antitumor Assays PMC - PMC8819302 OTO - NOTNLM OT - breast cancer OT - metastasis OT - mifepristone OT - paclitaxel OT - supramolecular hydrogel EDAT- 2021/12/04 06:00 MHDA- 2022/02/12 06:00 PMCR- 2022/02/01 CRDT- 2021/12/03 07:28 PHST- 2021/11/24 00:00 [revised] PHST- 2021/07/24 00:00 [received] PHST- 2021/11/28 00:00 [accepted] PHST- 2021/12/04 06:00 [pubmed] PHST- 2022/02/12 06:00 [medline] PHST- 2021/12/03 07:28 [entrez] PHST- 2022/02/01 00:00 [pmc-release] AID - CAS15230 [pii] AID - 10.1111/cas.15230 [doi] PST - ppublish SO - Cancer Sci. 2022 Feb;113(2):733-743. doi: 10.1111/cas.15230. Epub 2021 Dec 18.