Assembling synergistic peptide-drug conjugates for dual-targeted treatment of cancer metastasis. (October 2022)

• Record Type: Journal Article
• Authors: Yu, Xiunan; Wang, Hao; Liu, Xin; Huang, Le; Song, Na; Song, Yanqiu; Mo, Xiaowei; Lou, Shaofeng; Shi, Linqi; Yu, Zhilin
• Is Part Of: Nano today. Volume 46(2022)
• Publication Date: 2022-10
• Subjects: Peptide-drug conjugates -- Self-assembly -- Cancer metastasis -- Drug delivery -- Stimulus-response; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2022.101594
• Languages: English
• ISSNs: 1748-0132

Abstract

Abstract: We here report assembling synergistic peptide-drug conjugates (asPDCs) with the therapeutic activity arising from both peptide and chemodrug moieties for treatment of cancer metastasis. The asPDCs were created via co-assembling one protein-derived therapeutic peptide with its conjugate functionalized with paclitaxel (PTX), due to the strong assembling propensity of the peptide. While the asPDC showed the remarkable cytotoxicity against breast tumor cells due to the combinatorial effect, treatment of tumor cells with the asPDCs significantly inhibited cell migration and invasion through depolymerization of microfilaments and stabilization of microtubules by the peptide and PTX, respectively. In vivo results suggest the tumor-targeting property of the asPDCs and confirm their synergistic therapeutic roles in inhibition tumor growth and prevention of cancer metastasis. Our findings demonstrate the combining therapeutic effect and targeting property of the assembling synergistic peptide-drug conjugates, thus providing an alternative strategy for design of peptide-drug conjugates for disease treatment in the future. Graphical Abstract: ga1 Highlights: ● Creation of assembling synergistic peptide-drug conjugates (asPDCs) containing both therapeutic peptide and chemodrug. ● The resulting asPDCs forms well-defined nanostructures due to the strong assembling propensity of the peptide moiety. ● The asPDCs inhibit cell migration and invasion through depolymerizing microfilaments and stabilizing microtubules. ● Administration of the asPDCs allows for efficient prevention of in vivo tumor growth and cancer metastasis.