P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging

Abstract

Background 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. Methods Bone-targeted heptamethine cyanine fluorophores were synthesized by substituting the meso-carbon with a sulfur atom, resulting in a bathochromic shift and increased fluorescence intensity. The physicochemical, optical, and thermal stability of newly synthesized bone-targeted NIR fluorophores was performed in aqueous solvents. Calcium binding, bone-specific targeting, biodistribution, pharmacokinetics, and 2D and 3D NIR imaging were performed in animal models. Results 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. Particularly, P800SO3-PEG showed minimum nonspecific uptake, and most unbound molecules were excreted into the urinary bladder. Histological analyses demonstrated that P800SO3-PEG remained stable in the bone for over two weeks and was incorporated into bone matrices. Interestingly, the flexible thiol ethylene glycol linker on P800SO3-PEG induced a promising photothermal effect upon NIR laser irradiation, demonstrating potential theranostic imaging. Conclusions 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.

Bifunctional Tumor-Targeted Bioprobe for Phothotheranosis

“…1 C), indicating that cRGD-ZW800-PEG was rapidly decomposed upon NIR irradiation. Similar to ZW800-PEG, the overall electron density on the heptamethine chain of cRGD-ZW800-PEG increases due to the π-donation from the sulfur atom, which makes the heptamethine chain easier to undergo the oxidative addition with reactive singlet oxygen species [ 23 , 24 ].…”

Fluorescent Probes for the Detection of Bone Metabolism

“…Choi and coworkers integrated the specific segment of phosphonates into the non‐delocalized framework of heptamethine cyanine, resulting in a set of bone‐targeted NIR fluorescent probes 26 – 28 (Figure 7a). [56] Probes 26 – 28 exhibit a strong affinity for HAP and CP, enhancing their specificity for bone targeting, achieving a SBR surpassing 3.5.…”

Carboxyl-Modified Quantum Dots for NIR-IIb Bone Marrow Imaging

“…28−33 Choi et al utilized bisphosphonates to target hydroxyapatite and developed a small molecular fluorophore (emission: 1000 nm) for bone imaging. 34 More specifically, in the NIR-IIb window (1500− 1700 nm), light scattering is further reduced and autoluminescence is diminished, allowing for deeper penetration. 35−38 Zeng et al reported a poly(acrylic acid)-modified rare-earth nanoparticle at an emission wavelength of 1525 nm, displaying high affinity for bone.…”

“…Compared to the visible light and near-infrared I (NIR-I, 700–900 nm), NIR-II (1000–1700 nm) offers higher spatial resolution, greater penetration depths into biological substrates, lower optical absorption and scattering, and minimal tissue autofluorescence. − Hence, NIR-II imaging is increasingly researched due to its immense potential in preclinical studies and clinical applications. − Despite the limited studies currently conducted, NIR-II imaging undoubtedly holds significant potential for real-time monitoring and a more precise diagnosis of skeletal disorders. Recently, researchers developed rare-earth-based nanoparticles, gold nanoclusters, and small conjugated polymer nanoparticles for bone imaging, respectively. − Choi et al utilized bisphosphonates to target hydroxyapatite and developed a small molecular fluorophore (emission: 1000 nm) for bone imaging . More specifically, in the NIR-IIb window (1500–1700 nm), light scattering is further reduced and autoluminescence is diminished, allowing for deeper penetration. − Zeng et al reported a poly­(acrylic acid)-modified rare-earth nanoparticle at an emission wavelength of 1525 nm, displaying high affinity for bone .…”