Zhang Hongxia, Wang Yamei, Jiang Mengmeng, Wang Kunyu, Yan Jingru, Li Gongyu, Zheng Zhen
The 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.
Tianjin 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, China.
Mater Today Bio. 2025 Mar 20;32:101688. doi: 10.1016/j.mtbio.2025.101688. eCollection 2025 Jun.
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, and , 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. 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 , acts as both a sonosensitizer and ferroptosis inducer. Upon ultrasound irradiation, FP generates localized reactive oxygen species, further amplifying ferroptosis through enhanced lipid peroxidation. combined with ultrasound demonstrates potent antitumor efficacy and , 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.
癌症转移仍然是肿瘤学中的一项重大挑战，这促使人们探索创新的生物材料以提高治疗效果。虽然许多水凝胶仅作为被动载体，但本研究提出了两种新型自组装肽，[肽1]和[肽2]，它们形成具有内在抗转移特性的超分子水凝胶。我们证明了这些肽的纳米纤维形态与其增强的抗转移活性之间的相关性，这是由F-肌动蛋白组织的破坏以及影响与癌细胞粘附和肌动蛋白丝动力学相关的途径介导的。[实验]研究证实，使用4T1肺转移模型，肺转移显著减少。我们还证明了它们作为整合声动力疗法（SDT）和铁死亡的简单协同平台的潜力。掺入[肽2]的铁卟啉（FP）既是声敏剂又是铁死亡诱导剂。在超声照射下，FP产生局部活性氧，通过增强脂质过氧化进一步放大铁死亡。[肽2]与超声联合显示出强大的抗肿瘤功效，[肽1]和[肽2]促进细胞凋亡、铁死亡和免疫原性细胞死亡，导致肿瘤消退增强和强大的免疫激活。我们的研究结果突出了抗转移水凝胶作为一个有前途的多功能平台的潜力，以应对转移挑战，同时增强抗肿瘤免疫力。
