0587571 - ÚOCHB 2025 RIV US eng J - Článek v odborném periodiku
Hadzima, Martin - Faucher, F. F. - Blažková, K. - Yim, J. J. - Guerra, M. - Chen, S. - Woods, E. C. - Park, K. W. - Šácha, Pavel - Šubr, Vladimír - Kostka, Libor - Etrych, Tomáš - Majer, Pavel - Konvalinka, Jan - Bogyo, M.
Polymer-Tethered Quenched Fluorescent Probes for Enhanced Imaging of Tumor-Associated Proteases.
ACS Sensors. (2024). ISSN 2379-3694. E-ISSN 2379-3694
Grant CEP: GA MŠMT LX22NPO5102; GA MŠMT(CZ) EF18_053/0016940; GA MZd(CZ) NU21-08-00280; GA ČR(CZ) GA23-05642S
Institucionální podpora: RVO:61388963 ; RVO:61389013
Klíčová slova: fluorescence * imaging * protease * cancer * HPMA copolymer * iBody
Impakt faktor: 8.9, rok: 2022
Způsob publikování: Open access
https://doi.org/10.1021/acssensors.4c00912

Fluorescence-based contrast agents enable real-time detection of solid tumors and their neovasculature, making them ideal for use in image-guided surgery. Several agents have entered late-stage clinical trials or secured FDA approval, suggesting they are likely to become the standard of care in cancer surgeries. One of the key parameters to optimize in contrast agents is molecular size, which dictates much of the pharmacokinetic and pharmacodynamic properties of the agent. Here, we describe the development of a class of protease-activated quenched fluorescent probes in which a N-(2-hydroxypropyl)methacrylamide copolymer is used as the primary scaffold. This copolymer core provides a high degree of probe modularity to generate structures that cannot be achieved with small molecules and peptide probes. We used a previously validated cathepsin substrate and evaluated the effects of length and type of linker, as well as the positioning of the fluorophore/quencher pair on the polymer core. We found that the polymeric probes could be optimized to achieve increased overall signal and tumor-to-background ratios compared to the reference small molecule probe. Our results also revealed multiple structure-activity relationship trends that can be used to design and optimize future optical imaging probes. Furthermore, they confirm that a hydrophilic polymer is an ideal scaffold for use in optical imaging contrast probes, allowing a highly modular design that enables efficient optimization to maximize probe accumulation and overall biodistribution properties.
Trvalý link: https://hdl.handle.net/11104/0354701