Unimolecular Micellization Strategy for Achieving NIR-II Excited Fluorophores with Enhanced Brightness in Aqueous

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Abstract Fluorescence imaging in the second near-infrared window (NIR-II) is advantageous for the in situ detection of living organisms owing to its enhanced imaging depth and high spatial-temporal resolution. The development of high-performance fluorescence probes is crucial for enhancing imaging effectiveness. NIR-II (e.g. 1064 nm) excited molecular fluorophores exhibit favorable imaging performance and biocompatibility, but are susceptible to non-radiative decay, leading to substantial fluorescence quenching in aqueous compared to the NIR-I (e.g. 808 nm) excited counterparts. Previous studies have revealed that reducing the interaction between the excited-state center of the fluorophore and water molecules is a key point for improving fluorescence quantum yield (QY) in aqueous. Herein, an innovative unimolecular micellization strategy is proposed to achieve high-brightness organic fluorescence probes with NIR-II excitation (1064 nm) and emission (1000-1700 nm) in aqueous. We designed a series of NIR-II excited star-shaped amphiphilic molecules that demonstrate the ability to self-assemble into stable unimolecular micelles (UIMs) in aqueous. Upon unimolecular micellization, the intramolecular long alkyl chains can form a compact hydrophobic layer, effectively confining intermolecular interactions and shielding the excited-state center of the fluorophore from water-induced quenching, thereby maintaining high QY in aqueous. The IR-FCT8CP UIMs exhibit absorption and emission maximum wavelengths at 979 and 1181 nm, respectively, with a high QY of 0.0501% and a molar absorption coefficient of 1.67 × 104 M−1·cm−1 in aqueous, resulting in a brightness enhancement exceeding 28-fold compared to IR-FCDP UIMs. The exceptional fluorescence properties of IR-FCT8CP UIMs enable dynamic imaging of vessels using a 1500 nm long-pass filter, revealing a distinct vessel network with an optimal signal-to-background ratio. The concept of "unimolecular micellization for spatial confinement enhancement" offers innovative insights for developing NIR-II excited molecular fluorophores to maintain high brightness and stability in physiological environments for highly efficient bioimaging.
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Unimolecular Micellization Strategy for Achieving NIR-II Excited Fluorophores with Enhanced Brightness in Aqueous | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Unimolecular Micellization Strategy for Achieving NIR-II Excited Fluorophores with Enhanced Brightness in Aqueous Qinglai Yang, Zelong Li, Na Li, Sanlin Deng, Jinkang Zheng, Jian Zou, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6909767/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Fluorescence imaging in the second near-infrared window (NIR-II) is advantageous for the in situ detection of living organisms owing to its enhanced imaging depth and high spatial-temporal resolution. The development of high-performance fluorescence probes is crucial for enhancing imaging effectiveness. NIR-II (e.g. 1064 nm) excited molecular fluorophores exhibit favorable imaging performance and biocompatibility, but are susceptible to non-radiative decay, leading to substantial fluorescence quenching in aqueous compared to the NIR-I (e.g. 808 nm) excited counterparts. Previous studies have revealed that reducing the interaction between the excited-state center of the fluorophore and water molecules is a key point for improving fluorescence quantum yield (QY) in aqueous. Herein, an innovative unimolecular micellization strategy is proposed to achieve high-brightness organic fluorescence probes with NIR-II excitation (1064 nm) and emission (1000-1700 nm) in aqueous. We designed a series of NIR-II excited star-shaped amphiphilic molecules that demonstrate the ability to self-assemble into stable unimolecular micelles (UIMs) in aqueous. Upon unimolecular micellization, the intramolecular long alkyl chains can form a compact hydrophobic layer, effectively confining intermolecular interactions and shielding the excited-state center of the fluorophore from water-induced quenching, thereby maintaining high QY in aqueous. The IR-FCT8CP UIMs exhibit absorption and emission maximum wavelengths at 979 and 1181 nm, respectively, with a high QY of 0.0501% and a molar absorption coefficient of 1.67 × 104 M−1·cm−1 in aqueous, resulting in a brightness enhancement exceeding 28-fold compared to IR-FCDP UIMs. The exceptional fluorescence properties of IR-FCT8CP UIMs enable dynamic imaging of vessels using a 1500 nm long-pass filter, revealing a distinct vessel network with an optimal signal-to-background ratio. The concept of "unimolecular micellization for spatial confinement enhancement" offers innovative insights for developing NIR-II excited molecular fluorophores to maintain high brightness and stability in physiological environments for highly efficient bioimaging. Biological sciences/Biological techniques/Imaging/Fluorescence imaging Physical sciences/Nanoscience and technology/Nanobiotechnology/Nanoparticles Near-infrared II Molecular Fluorophores Unimolecular Micellization Strategy Anti-quenching Quantum Yields Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.pdf Supplementary Information for main text Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6909767","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":473051203,"identity":"f760b421-a664-4b85-876d-52e18a03d15e","order_by":0,"name":"Qinglai 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