![]() ![]() ![]() ![]() We modified previously developed NIR fluorophores to generate a renal clearable bone-targeted contrast agent with improved optical properties and biodistribution, in addition to enabling a photothermal effect (Fig. Here we designed targeted NIR fluorophores for noninvasive imaging of bone tissue based on the structure-inherent targeting (SIT) strategy, in which targeting moieties or pharmacophores are incorporated into the chemical structure of a fluorophore. However, unfortunately, there is no bone-specific NIR-II imaging probe that enables real-time noninvasive detection of bone growth and tissue microcalcification. Due to the finer structure of bone and the inherent limitations of conventional imaging modalities, NIR-II imaging has the potential to obtain high-resolution bone diagnostics for use in clinical applications. It is worth noting that the classical NIR-I fluorophore, indocyanine green (ICG), has been explored for NIR-II tail imaging of various cancerous tissues in the clinic. Compared to the traditional NIR imaging (NIR-Ia, 650–900 nm), the NIR-II window (1,000–1,700 nm) is more attractive due to its ability for deeper light penetration and lower tissue scattering, resulting in enhanced signal-to-background ratios (SBR). Near-infrared (NIR) fluorescence imaging is an emerging technology well suited to studying the functional and structural aspects of bone diseases due to the reduced tissue absorption and scattering of NIR light and minimum autofluorescence. Furthermore, the advancement in optical imaging systems and contrast agents enables us to view the detailed changes in bones with high spatiotemporal resolution wide-field imaging. Traditional bone imaging modalities such as X-ray radiogrammetry, computed tomography, quantitative ultrasound, position emission tomography, and magnetic resonance imaging, are routinely used for the inspection of bone fractures, injuries, and joint abnormalities. Noninvasive imaging technology allows for the visualization of bone growth, abnormalities, and metabolism, while playing an integral role in image-guided interventions and surgical procedures of the bones. P800SO3-PEG shows a high affinity for bone tissues, deeper tissue imaging capabilities, minimum nonspecific uptake in the major organs, and photothermal effect upon laser irradiation, making it optimal for bone-targeted theranostic imaging. Interestingly, the flexible thiol ethylene glycol linker on P800SO3-PEG induced a promising photothermal effect upon NIR laser irradiation, demonstrating potential theranostic imaging. Histological analyses demonstrated that P800SO3-PEG remained stable in the bone for over two weeks and was incorporated into bone matrices. Particularly, P800SO3-PEG showed minimum nonspecific uptake, and most unbound molecules were excreted into the urinary bladder. The newly synthesized S-substituted heptamethine fluorophores demonstrated a high affinity for hydroxyapatite and calcium phosphate, which improved bone-specific targeting with signal-background ratios > 3.5. Calcium binding, bone-specific targeting, biodistribution, pharmacokinetics, and 2D and 3D NIR imaging were performed in animal models. The physicochemical, optical, and thermal stability of newly synthesized bone-targeted NIR fluorophores was performed in aqueous solvents. Methodsīone-targeted heptamethine cyanine fluorophores were synthesized by substituting the meso-carbon with a sulfur atom, resulting in a bathochromic shift and increased fluorescence intensity. Due to the deep tissue penetration and reduced scattering, NIR-II fluorescence imaging is advantageous over conventional visible and NIR-I fluorescence imaging for the detection of bone growth, metabolism, metastasis, and other bone-related diseases. ![]()
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