Paclitaxel‐based supramolecular hydrogel loaded with mifepristone for the inhibition of breast cancer metastasis

• Published in: Cancer science 2022-02, Vol.113 (2), p.733-743
• Main Authors: Zhao, Cui‐Cui, Zhang, Chuan‐Gui, Sun, Xuan, Guo, Qingxiang, Liu, Jinjian, Liu, Yan, Hao, Ya‐Nan, Feng, Guowei, Yang, Lijun, Liu, Hong, Liu, Jianfeng
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Biocompatibility; Biological Availability; Blood; Blood circulation; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cancer therapies; Cell Line, Tumor; Cell Movement - drug effects; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug Carriers - therapeutic use; Drug Liberation; Drugs; Female; Glucocorticoids; Humans; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Hydrogels - therapeutic use; Laboratory animals; Mass spectrometry; Metastases; Metastasis; Mice; Mifepristone; Mifepristone - chemistry; Mifepristone - pharmacology; Mifepristone - therapeutic use; Nanomaterials; Nanostructures - therapeutic use; NMR; Nuclear magnetic resonance; Original; Paclitaxel; Paclitaxel - chemistry; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Pharmacokinetics; Protein-tyrosine kinase receptors; Scientific imaging; Statistical analysis; supramolecular hydrogel; Tumor Burden - drug effects; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15230

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. A novel supramolecular hydrogel coloaded with paclitaxel and mifepristone has good water solubility, fine cell uptake, and biosafety. It can significantly limit the metastasis of breast cancer in vitro and in vivo. It might act by mifepristone/glucocorticoid receptor/ROR1 and MMPs.