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

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 α_vβ₃-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.

SUBMITTER: Chen J

PROVIDER: S-EPMC6685945 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Chen Junyi J Ni Hanzhi H Meng Zhao Z Wang Jing J Huang Xiayang X Dong Yansheng Y Sun Chao C Zhang Yadan Y Cui Lei L Li Jian J Jia Xueshun X Meng Qingbin Q Li Chunju C

Nature communications 20190807 1

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 ...[more]

PMID: 31391464

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Project description:BackgroundImproved surveillance techniques are required to accelerate efforts against major arthropod-borne diseases such as malaria, dengue, filariasis, Zika and yellow-fever. Light-emitting diodes (LEDs) are increasingly used in mosquito traps because they improve energy efficiency and battery longevity relative to incandescent bulbs. This study evaluated the efficacy of a new ultraviolet LED trap (Mosclean) against standard mosquito collection methods.MethodsThe study was conducted in controlled semi-field settings and in field conditions in rural south-eastern Tanzania. The Mosclean trap was compared to commonly used techniques, namely CDC-light traps, human landing catches (HLCs), BG-Sentinel traps and Suna traps.ResultsWhen simultaneously placed inside the same semi-field chamber, the Mosclean trap caught twice as many Anopheles arabiensis as the CDC-light trap, and equal numbers to HLCs. Similar results were obtained when traps were tested individually in the chambers. Under field settings, Mosclean traps caught equal numbers of An. arabiensis and twice as many Culex mosquitoes as CDC-light traps. It was also better at trapping malaria vectors compared to both Suna and BG-Sentinel traps, and was more efficient in collecting mosquitoes indoors than outdoors. The majority of An. arabiensis females caught by Mosclean traps were parous (63.6%) and inseminated (89.8%). In comparison, the females caught by CDC-light traps were 43.9% parous and 92.8% inseminated.ConclusionsThe UV LED trap (Mosclean trap) was efficacious for sampling Anopheles and Culex mosquitoes. Its efficacy was comparable to and in some instances better than traps commonly used for vector surveillance. The Mosclean trap was more productive in sampling mosquitoes indoors compared to outdoors. The trap can be used indoors near human-occupied nets, or outdoors, in which case additional CO2 improves catches. We conclude that this trap may have potential for mosquito surveillance. However, we recommend additional field tests to validate these findings in multiple settings and to assess the potential of LEDs to attract non-target organisms, especially outdoors.

Dataset Information

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

Publications

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

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