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Abstract: Particle size is an important physical parameter in any nanomaterial designed for biomedical applications. It critically influences the biological fate of nanoparticles. It is generally believed that a range between 10 and 200 nm is most relevant to physical and biochemical targeting through both intravascular and site-specific deliveries.1 High porosity, purely organic nature, structural tunability and the ability to gradually release therapeutically-relevant cargo have rendered covalent organic frameworks (COFs) promising materials in biomedical research. While several COF-based drug delivery systems have been reported, particle aggregation and the associated particle size pose a significant barrier to real-life implementation of these systems.2 In the current talk, two strategies to address these issues will be presented as they have been applied to biosensing and delivery applications. Firstly, prolonged ultrasonication has proven an effective method of reducing the COF particle size while maintaining the material’s chemical properties.3 A fluorescent COF, that was post-synthetically modified to incorporate a hypoxia-targeting nitroimidazole moiety, was exposed to prolonged ultrasonication which effectively reduced the particle size from several µm to <170 nm.4 The ultrasonication treatment did not significantly hamper the material’s physical or chemical properties, such as crystallinity, and it even enhanced its fluorescence signal by overcoming aggregation-caused quenching (ACQ). The material and its constituent building blocks were shown to have minimal or no cytotoxicity. The COF’s internalization was monitored by fluorescence spectroscopy, and it preferentially accumulated in cells exposed to hypoxic environment, thus serving as a fluorescent biosensor for hypoxia. Another strategy of limiting the COF particle size is to grow the material on nano-sized substrates. Silver nanowires (AgNWs) have been shown as effective intracellular sensors5 and single-cell endoscopic tools.6 We have prepared AgNWs with diameters below 200 nm and have employed various synthetic methods to coat them with thiol-functionalized COFs. Favorable coordination bonds that form between Ag and the thiol functional group in the COF linkers drive the assembly process. Both bottom-up synthetic approaches, where the COF is grown on the surface of AgNWs, and top-down strategies, where pre-synthesized COF particles are attached onto AgNWs surface have been successful. The inorganic-organic hybrid materials were characterized by various techniques, including electron microscopy, Fourier-transform infrared spectroscopy, thermogravimetric analysis, and powder X-ray diffraction. All characterizations combined suggest that the diameter of the COF-coated AgNWs remains well in the nanometer-size regime. References: (1) Hickey, J. W.; Santos, J. L.; Williford, J.-M.; Mao, H.-Q. Control of Polymeric Nanoparticle Size to Improve Therapeutic Delivery. J. Control. Release 2015, 219, 536–547. (2) Esrafili, A.; Wagner, A.; Inamdar, S.; Acharya, A. P. Covalent Organic Frameworks for Biomedical Applications. Adv. Healthc. Mater. 2021, 10 (6), 2002090. (3) Skorjanc, T.; Heinrich, J.; Makuc, D.; Kulak, N.; Valant, M. Sustained Delivery of Cu(II)-Based DNA Intercalators by Nanometer-Sized Cyclodextrin-Based Porous Polymers. ACS Appl. Nano Mater. 2023, 6 (22), 21162–21168. (4) Skorjanc, T.; Shetty, D.; Kumar, S.; Makuc, D.; Mali, G.; Volavšek, J.; Bergant Marušič, M.; Valant, M. Nitroreductase-Sensitive Fluorescent Covalent Organic Framework for Tumor Hypoxia Imaging in Cells. Chem. Commun. 2023, 59 (38), 5753–5756. (5) Zhang, Q.; Inose, T.; Ricci, M.; Li, J.; Tian, Y.; Wen, H.; Toyouchi, S.; Fron, E.; Ngoc Dao, A. T.; Kasai, H.; Rocha, S.; Hirai, K.; Fortuni, B.; Uji-i, H. Gold-Photodeposited Silver Nanowire Endoscopy for Cytosolic and Nuclear PH Sensing. ACS Appl. Nano Mater. 2021, 4 (9), 9886–9894. (6) Ricci, M.; Fortuni, B.; Vitale, R.; Zhang, Q.; Fujita, Y.; Toyouchi, S.; Lu, G.; Rocha, S.; Inose, T.; Uji-I, H. Gold-Etched Silver Nanowire Endoscopy: Toward a Widely Accessible Platform for Surface-Enhanced Raman Scattering-Based Analysis in Living Cells. Anal. Chem. 2021, 93 (12), 5037–5045.
Keywords: covalent organic frameworks, imaging, delivery, nanoendoscopy, nanowire
Published in RUNG: 22.07.2024; Views: 1796; Downloads: 3
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Abstract: Fluorescent covalent organic frameworks (COFs) have emerged as promising candidates for imaging living cells due to their unique properties and adjustable fluorescence. In this mini-review, we provide an overview of recent advancements in fluorescent COFs for bioimaging applications. We discuss the strategies used to design COFs with desirable properties such as high photostability, excellent biocompatibility, and pH sensitivity. Additionally, we explore the various ways in which fluorescent COFs are utilized in bioimaging, including cellular imaging, targeting specific organelles, and tracking biomolecules. We delve into their applications in sensing intracellular pH, reactive oxygen species (ROS), and specific biomarkers. Furthermore, we examine how functionalization techniques enhance the targeting and imaging capabilities of fluorescent COFs. Finally, we discuss the challenges and prospects in the field of fluorescent COFs for bioimaging in living cells, urging further research in this exciting area.
Keywords: covalent organic frameworks, fluorescent materials, imaging, bioimaging, biosensors
Published in RUNG: 05.03.2024; Views: 2463; Downloads: 8
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Abstract: Hypoxia refers to a condition where cells and tissues experience low, inadequate levels of O2. While healthy tissues are typically supplied with sufficient O2 (normoxia), cancerous tissues commonly face hypoxia due to the tumor’s extraordinarily high demand for oxygen. Various fluorescent small-molecule probes have been designed for selective detection of hypoxia in living cells, but few nanomaterials have been investigated for this type of bioimaging. Herein, we prepare a fluorescent covalent organic framework (COF) with β-ketoenamine linkages and post-synthetically modify it to conjugate hypoxia-sensitive nitroimidazole moieties into its pores (NI-COF). Stacks of sheets in NI-COF observed under electron microscopy were exfoliated by ultrasonication, and dynamic light scattering measurements confirmed particle size of less than 200 nm. Thus-prepared material exhibited good stability in physiological conditions and low cytotoxicity in in vitro experiments. NI-COF also showed useful fluorescence properties with an emission peak at 490 nm (λex = 420 nm) at both neutral and mildly acidic pH levels that are characteristic of tumor tissues. Encouraged by the favorable properties of the material, we incubated HeLa cells pre-treated in either hypoxic or normoxic conditions with NI-COF. Fluorescence microscopy images demonstrated that the material was preferentially taken up by hypoxic cells, which showed higher fluorescence signal in their interior than cells cultured under normoxia conditions. It is anticipated that this study will stimulate further developments of COFs for imaging various biological conditions.
Keywords: hypoxia, fluorescence, covalent organic frameworks, imaging, tumor cells
Published in RUNG: 19.09.2023; Views: 2444; Downloads: 8
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Abstract: Porous organic polymers (POPs) and covalent organic frameworks (COFs) have gained significant attention in the scientific community for a wide array of applications because of their attractive physical and chemical properties. Porosity of these materials provides ample surface area for interaction with targets, while crystallinity allows for highly specific structural tuning. In this seminar, I will present two strategies of utilizing these features of newly prepared materials in biosensing. Firstly, a cationic POP was synthesized, deposited onto interdigitated electrode arrays via a nontraditional electrophoresis technique, and utilized for electrochemical sensing of bacterial cells. As the principle of detection relied on electrostatic interactions between the cationic POP and the anionic bacterial surface, the sensor operated for both Gram-positive and Gram-negative bacteria. Secondly, a small-molecule nitroimidazole target for hypoxia, a low oxygen environment present in tumors, was post-synthetically conjugated to the pores of a fluorescent COF. This material served as a useful hypoxia imaging agent in cancerous cells. The seminar will conclude with some future perspectives on POPs and COFs in biological applications followed by Q & A.
Keywords: Porous organic polymers, covalent organic frameworks, biosensors, hypoxia
Published in RUNG: 13.07.2023; Views: 2464; Downloads: 0
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Keywords: covalent organic frameworks, imaging, hypoxia, fluorescence, cancer cells
Published in RUNG: 17.05.2023; Views: 2826; Downloads: 22
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