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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\u2010neoplastic properties of two distinct imine\u2010based nCOFs. The approach involved an in\u2010depth 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\u2010related 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.<\/jats:p>","DOI":"10.1002\/advs.202407391","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T09:21:38Z","timestamp":1728552098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Insights into the Biological Activity and Bio\u2010Interaction Properties of Nanoscale Imine\u2010Based 2D and 3D Covalent Organic Frameworks"],"prefix":"10.1002","volume":"11","author":[{"given":"Hao","family":"Ye","sequence":"first","affiliation":[{"name":"Multi\u2010Scale Robotics Lab (MSRL) Institute of Robotics &amp; Intelligent Systems (IRIS) ETH Zurich  Zurich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3385-2851","authenticated-orcid":false,"given":"Carlos","family":"Franco","sequence":"additional","affiliation":[{"name":"Multi\u2010Scale Robotics Lab (MSRL) Institute of Robotics &amp; Intelligent Systems (IRIS) ETH Zurich  Zurich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa A.","family":"Aboouf","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Zurich  Winterthurerstrasse 260 Zurich 8057 Switzerland"},{"name":"Department of Biochemistry Faculty of Pharmacy Ain Shams University  Cairo 11566 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Thiersch","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Zurich  Winterthurerstrasse 260 Zurich 8057 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Semih","family":"Sevim","sequence":"additional","affiliation":[{"name":"Multi\u2010Scale Robotics Lab (MSRL) Institute of Robotics &amp; Intelligent Systems (IRIS) ETH Zurich  Zurich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Llacer\u2010Wintle","sequence":"additional","affiliation":[{"name":"Multi\u2010Scale Robotics Lab (MSRL) Institute of Robotics &amp; Intelligent Systems (IRIS) ETH Zurich  Zurich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Veciana","sequence":"additional","affiliation":[{"name":"Multi\u2010Scale Robotics Lab (MSRL) Institute of Robotics &amp; Intelligent Systems (IRIS) ETH Zurich  Zurich 8092 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Llaurad\u00f3\u2010Capdevila","sequence":"additional","affiliation":[{"name":"Departament de Ci\u00e8ncia dels Materials i Qu\u00edmica F\u00edsica Institut de Qu\u00edmica Te\u00f2rica i Computacional University of Barcelona  Barcelona 08028 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics Wuya College of Innovation Shenyang Pharmaceutical University  103 Wenhua Road Shenyang Liaoning 110016 P. 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