Homomultivalent Polymeric Nanotraps Disturb Lipid Metabolism Homeostasis and Tune Pyroptosis in Cancer
© 2024 Wiley‐VCH GmbH.
| Publié dans: | Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 15 vom: 01. Apr., Seite e2312528 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2024
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| Accès à la collection: | Advanced materials (Deerfield Beach, Fla.) |
| Sujets: | Journal Article homomultivalent lipid metabolism nanotraps polymeric β‐cyclodextrin pyroptosis 2,2,3,3-tetramethylcyclopropane carboxamide Cholesterol 97C5T2UQ7J Polymers plus... |
| Résumé: | © 2024 Wiley‐VCH GmbH. Genetic manipulations and pharmaceutical interventions to disturb lipid metabolism homeostasis have emerged as an attractive approach for the management of cancer. However, the research on the utilization of bioactive materials to modulate lipid metabolism homeostasis remains constrained. In this study, heptakis (2,3,6-tri-O-methyl)-β-cyclodextrin (TMCD) is utilized to fabricate homomultivalent polymeric nanotraps, and surprisingly, its unprecedented ability to perturb lipid metabolism homeostasis and induce pyroptosis in tumor cells is found. Through modulation of the density of TMCD arrayed on the polymers, one top-performing nanotrap, PTMCD4, exhibits the most powerful cholesterol-trapping and depletion capacity, thus achieving prominent cytotoxicity toward different types of tumor cells and encouraging antitumor effects in vivo. The interactions between PTMCD4 and biomembranes of tumor cells effectively enable the reduction of cellular phosphatidylcholine and cholesterol levels, thus provoking damage to the biomembrane integrity and perturbation of lipid metabolism homeostasis. Additionally, the interplays between PTMCD4 and lysosomes also induce lysosomal stress, activate the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasomes, and subsequently trigger tumor cell pyroptosis. To sum up, this study first introduces dendronized bioactive polymers to manipulate lipid metabolism and has shed light on another innovative insight for cancer therapy |
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| Description: | Date Completed 15.04.2024 Date Revised 06.05.2024 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-4095 |
| DOI: | 10.1002/adma.202312528 |