10.6084/M9.FIGSHARE.C.6227405
Haoran Wang
Haoran
Wang
Harvard University
Shenyang Pharmaceutical University
Homan Kang
Homan
Kang
Harvard University
Jason Dinh
Jason
Dinh
Harvard University
Shinya Yokomizo
Shinya
Yokomizo
Harvard University
Wesley R. Stiles
Wesley R.
Stiles
Harvard University
Molly Tully
Molly
Tully
Harvard University
Kevin Cardenas
Kevin
Cardenas
Harvard University
Surbhi Srinivas
Surbhi
Srinivas
Harvard University
Jason Ingerick
Jason
Ingerick
Harvard University
Sung Ahn
Sung
Ahn
Harvard University
Kai Bao
Kai
Bao
Harvard University
Hak Soo Choi
Hak Soo
Choi
0000-0002-7982-6483
Harvard University
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.
Biophysics
Biochemistry
Space Science
Physical Sciences not elsewhere classified
Medicine
Cell Biology
Physiology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Sociology
Cancer
figshare
2022
2022-10-02
2022-10-02
Collection
CC BY 4.0