Self-Assembled Core–Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition
Xiang Zhang, Cheng-Hao Xu, Juan Mo, Xiu‐Jing Zheng, Yanfang Chen, An-Qi Yang, Yiheng Zhang, Pengyu Wang, Xia Yuan, Xin‐Shan Ye
Abstract
Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.