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P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging
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 c...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526902/ https://www.ncbi.nlm.nih.gov/pubmed/36183117 http://dx.doi.org/10.1186/s40824-022-00294-2 |
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author | Wang, Haoran Kang, Homan Dinh, Jason Yokomizo, Shinya Stiles, Wesley R. Tully, Molly Cardenas, Kevin Srinivas, Surbhi Ingerick, Jason Ahn, Sung Bao, Kai Choi, Hak Soo |
author_facet | Wang, Haoran Kang, Homan Dinh, Jason Yokomizo, Shinya Stiles, Wesley R. Tully, Molly Cardenas, Kevin Srinivas, Surbhi Ingerick, Jason Ahn, Sung Bao, Kai Choi, Hak Soo |
author_sort | Wang, Haoran |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40824-022-00294-2. |
format | Online Article Text |
id | pubmed-9526902 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-95269022022-10-03 P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging Wang, Haoran Kang, Homan Dinh, Jason Yokomizo, Shinya Stiles, Wesley R. Tully, Molly Cardenas, Kevin Srinivas, Surbhi Ingerick, Jason Ahn, Sung Bao, Kai Choi, Hak Soo Biomater Res Research Article 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40824-022-00294-2. BioMed Central 2022-10-01 /pmc/articles/PMC9526902/ /pubmed/36183117 http://dx.doi.org/10.1186/s40824-022-00294-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Wang, Haoran Kang, Homan Dinh, Jason Yokomizo, Shinya Stiles, Wesley R. Tully, Molly Cardenas, Kevin Srinivas, Surbhi Ingerick, Jason Ahn, Sung Bao, Kai Choi, Hak Soo P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title | P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title_full | P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title_fullStr | P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title_full_unstemmed | P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title_short | P800SO3-PEG: a renal clearable bone-targeted fluorophore for theranostic imaging |
title_sort | p800so3-peg: a renal clearable bone-targeted fluorophore for theranostic imaging |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9526902/ https://www.ncbi.nlm.nih.gov/pubmed/36183117 http://dx.doi.org/10.1186/s40824-022-00294-2 |
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