Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

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.

• Authors: Xiang Zhang, Cheng-Hao Xu, Juan Mo, Xiu-Jing Zheng, Yan-Fang Chen, An-Qi Yang, Yi-Heng Zhang, Peng-Yu Wang, Xia Yuan, Xin-Shan Ye
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 15 Issue 6 Pg. 7713-7724 (Feb 15 2023) ISSN: 1944-8252 [Electronic] United States
• PMID: 36728365 (Publication Type: Journal Article)

Chemical References

• Polymers
• Sialyltransferases

Topics

• Animals
• Polymers
• Nanoparticles
• Lung Neoplasms (drug therapy)
• Sialyltransferases
• Sexually Transmitted Diseases