Supramolecular trap for catching polyamines in cells as an anti-tumor strategy

Junyi Chen, Hanzhi Ni, Zhao Meng, Jing Wang, Xiayang Huang, Yansheng Dong, Chao Sun, Yadan Zhang, Lei Cui, Jian Li, Xueshun Jia, Qingbin Meng () and Chunju Li ()
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Junyi Chen: Shanghai University
Hanzhi Ni: Beijing Institute of Pharmacology and Toxicology
Zhao Meng: Beijing Institute of Pharmacology and Toxicology
Jing Wang: Beijing Institute of Pharmacology and Toxicology
Xiayang Huang: Shanghai University
Yansheng Dong: Beijing Institute of Pharmacology and Toxicology
Chao Sun: Beijing Institute of Pharmacology and Toxicology
Yadan Zhang: Beijing Institute of Pharmacology and Toxicology
Lei Cui: Shanghai University
Jian Li: Shanghai University
Xueshun Jia: Shanghai University
Qingbin Meng: Beijing Institute of Pharmacology and Toxicology
Chunju Li: Shanghai University

Nature Communications, 2019, vol. 10, issue 1, 1-8

Abstract: Abstract Polyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host–guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N3)EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin αvβ3-overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 105–106 M−1. We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.

Date: 2019
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DOI: 10.1038/s41467-019-11553-7

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