Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy

Cancer metastasis remains a significant challenge in oncology, prompting the exploration of innovative biomaterials to enhance treatment efficacy. While many hydrogels only serve as passive carriers, this study presents two novel self-assembling peptides, CWEWTWY and NapFFSGP, which form supramolecu...

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Main Authors: Hongxia Zhang, Yamei Wang, Mengmeng Jiang, Kunyu Wang, Jingru Yan, Gongyu Li, Zhen Zheng
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S2590006425002479
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author Hongxia Zhang
Yamei Wang
Mengmeng Jiang
Kunyu Wang
Jingru Yan
Gongyu Li
Zhen Zheng
author_facet Hongxia Zhang
Yamei Wang
Mengmeng Jiang
Kunyu Wang
Jingru Yan
Gongyu Li
Zhen Zheng
author_sort Hongxia Zhang
collection DOAJ
description Cancer metastasis remains a significant challenge in oncology, prompting the exploration of innovative biomaterials to enhance treatment efficacy. While many hydrogels only serve as passive carriers, this study presents two novel self-assembling peptides, CWEWTWY and NapFFSGP, which form supramolecular hydrogels with intrinsic anti-metastatic properties. We demonstrate a correlation between the nanofibrous morphology of these peptides and their enhanced anti-metastatic activity, mediated by disruption of F-actin organization and impacting pathways related to cancer cell adhesion and actin filament dynamics. In vivo studies confirm a significant reduction in lung metastasis using a 4T1 pulmonary metastasis model. We also demonstrate their potential as a simple, synergistic platform integrating sonodynamic therapy (SDT) and ferroptosis. Ironporphyrin (FP), incorporated into Gel@FP, acts as both a sonosensitizer and ferroptosis inducer. Upon ultrasound irradiation, FP generates localized reactive oxygen species, further amplifying ferroptosis through enhanced lipid peroxidation. Gel@FP combined with ultrasound demonstrates potent antitumor efficacy in vitro and in vivo, promoting apoptosis, ferroptosis, and immunogenic cell death, leading to enhanced tumor regression and robust immune activation. Our findings highlight the potential of anti-metastatic hydrogels as a promising multifunctional platform to address the challenges of metastasis while enhancing antitumor immunity.
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spelling doaj-art-7112b61a6c4e4f938562a59cbc8a56d82025-08-20T03:39:57ZengElsevierMaterials Today Bio2590-00642025-06-013210168810.1016/j.mtbio.2025.101688Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapyHongxia Zhang0Yamei Wang1Mengmeng Jiang2Kunyu Wang3Jingru Yan4Gongyu Li5Zhen Zheng6The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, ChinaTianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, ChinaThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, ChinaThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, ChinaThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, ChinaTianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Science, Frontiers Science Center for New Organic Matter, College of Chemistry, Nankai University, Tianjin, 300071, ChinaThe Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, China; Corresponding author.Cancer metastasis remains a significant challenge in oncology, prompting the exploration of innovative biomaterials to enhance treatment efficacy. While many hydrogels only serve as passive carriers, this study presents two novel self-assembling peptides, CWEWTWY and NapFFSGP, which form supramolecular hydrogels with intrinsic anti-metastatic properties. We demonstrate a correlation between the nanofibrous morphology of these peptides and their enhanced anti-metastatic activity, mediated by disruption of F-actin organization and impacting pathways related to cancer cell adhesion and actin filament dynamics. In vivo studies confirm a significant reduction in lung metastasis using a 4T1 pulmonary metastasis model. We also demonstrate their potential as a simple, synergistic platform integrating sonodynamic therapy (SDT) and ferroptosis. Ironporphyrin (FP), incorporated into Gel@FP, acts as both a sonosensitizer and ferroptosis inducer. Upon ultrasound irradiation, FP generates localized reactive oxygen species, further amplifying ferroptosis through enhanced lipid peroxidation. Gel@FP combined with ultrasound demonstrates potent antitumor efficacy in vitro and in vivo, promoting apoptosis, ferroptosis, and immunogenic cell death, leading to enhanced tumor regression and robust immune activation. Our findings highlight the potential of anti-metastatic hydrogels as a promising multifunctional platform to address the challenges of metastasis while enhancing antitumor immunity.http://www.sciencedirect.com/science/article/pii/S2590006425002479Supramolecular hydrogelAnti-metastasisSelf-assembly peptideSonodynamic therapyFerroptosis
spellingShingle Hongxia Zhang
Yamei Wang
Mengmeng Jiang
Kunyu Wang
Jingru Yan
Gongyu Li
Zhen Zheng
Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
Materials Today Bio
Supramolecular hydrogel
Anti-metastasis
Self-assembly peptide
Sonodynamic therapy
Ferroptosis
title Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
title_full Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
title_fullStr Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
title_full_unstemmed Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
title_short Inherently anti-metastatic peptide hydrogels for sonodynamic-amplified ferroptosis in cancer therapy
title_sort inherently anti metastatic peptide hydrogels for sonodynamic amplified ferroptosis in cancer therapy
topic Supramolecular hydrogel
Anti-metastasis
Self-assembly peptide
Sonodynamic therapy
Ferroptosis
url http://www.sciencedirect.com/science/article/pii/S2590006425002479
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