Bimetallic Nanoplatforms for Prostate Cancer Treatment by Interfering Cellular Communication
Siyang Zhang, Xiuru Ji, Zeyang Liu, Zhiwen Xie, Yue Wang, Han Wang, Dalong Ni
Abstract
Cellular communication mediated by messenger molecules plays an important role in the progression of cancer. Herein, pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) loaded with PtCl 2 (OH) 2 (NH 3 ) 2 [i.e., Pt(IV)] bimetallic nanoplatforms were developed for prostate cancer therapy by interfering inositol-1, 4, 5-trisphosphate (IP3)-mediated cellular communication. As an important messenger in cells, the function of IP3 was found to be efficiently interfered with by the Pt(IV)-binding inositol unit. This finding effect of Pt(IV) is totally different from its traditional function as a prodrug of cis -platinum for chemotherapy. The decreased IP3 signal further downregulated the cytoplasmic Ca 2+ concentration and downstream signal transduction to inhibit proliferation and invasion of tumor cells. Meanwhile, Zn 2+ released from ZIF-8 under an acidic tumor microenvironment decreased adenosine triphosphate biosynthesis, which could further limit the cellular communication. Such a proposed strategy of interfering cellular communication has demonstrated its feasibility in this study, which may provide new perspectives for cancer therapy.