Multi-Scale Robotics Lab (MSRL), Institute of Robotics & Intelligent Systems (IRIS), ETH Zurich, Zurich, 8092, Switzerland.
Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich, 8057, Switzerland.
Adv Sci (Weinh). 2024 Nov;11(44):e2407391. doi: 10.1002/advs.202407391. Epub 2024 Oct 10.
Covalent Organic Frameworks (COFs) emerged as versatile materials with promising potential in biomedicine. Their customizable functionalities and tunable pore structures make them valuable for various biomedical applications such as biosensing, bioimaging, antimicrobial activity, and targeted drug delivery. Despite efforts made to create nanoscale COFs (nCOFs) to enhance their interaction with biological systems, a comprehensive understanding of their inherent biological activities remains a significant challenge. In this study, a thorough investigation is conducted into the biocompatibility and anti-neoplastic properties of two distinct imine-based nCOFs. The approach involved an in-depth analysis of these nCOFs through in vitro experiments with various cell types and in vivo assessments using murine models. These findings revealed significant cytotoxic effects on tumor cells. Moreover, the activation of multiple cellular death pathways, including apoptosis, necroptosis, and ferroptosis is determined, supported by evidence at the molecular level. In vivo evaluations exhibited marked inhibition of tumor growth, associated with the elevated spontaneous accumulation of nCOFs in tumor tissues and the modulation of cell death-related protein expression. The research contributes to developing a roadmap for the characterization of the intricate interactions between nCOFs and biological systems and opens new avenues for exploiting their therapeutic potential in advanced biomedical applications.
共价有机框架（COFs）作为多功能材料，在生物医药领域具有广阔的应用前景。它们可定制的功能和可调的孔结构，使它们在生物传感、生物成像、抗菌活性和靶向药物输送等各种生物医学应用中具有重要价值。尽管已经努力创造了纳米级 COFs（nCOFs）以增强它们与生物系统的相互作用，但对其固有生物活性的全面理解仍然是一个重大挑战。在这项研究中，我们深入研究了两种不同的亚胺基 nCOFs 的生物相容性和抗肿瘤特性。该方法通过在各种细胞类型的体外实验和使用小鼠模型的体内评估，对这些 nCOFs 进行了深入分析。这些发现表明它们对肿瘤细胞具有显著的细胞毒性作用。此外，通过分子水平的证据，确定了多种细胞死亡途径的激活，包括细胞凋亡、坏死性凋亡和铁死亡。体内评估显示出对肿瘤生长的显著抑制作用，这与 nCOFs 在肿瘤组织中的自发积累增加以及细胞死亡相关蛋白表达的调节有关。该研究为研究 nCOFs 与生物系统之间复杂的相互作用提供了路线图，并为在先进的生物医学应用中开发它们的治疗潜力开辟了新途径。
