Novel bidentate β-glutamic acid-based bone-targeting agents for in vivo bone imaging
- Authors
- Park, J.S.; Lim, Y.G.; Park, Kyeongsoon
- Issue Date
- Jun-2022
- Publisher
- Korean Society of Industrial Engineering Chemistry
- Keywords
- Bone targeting imaging; Fluorescence imaging; Hydroxyapatite; β-Glutamic acid
- Citation
- Journal of Industrial and Engineering Chemistry, v.110, pp 471 - 478
- Pages
- 8
- Journal Title
- Journal of Industrial and Engineering Chemistry
- Volume
- 110
- Start Page
- 471
- End Page
- 478
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/56664
- DOI
- 10.1016/j.jiec.2022.03.021
- ISSN
- 1226-086X
1876-794X
- Abstract
- Due to the unique calcium mineral composition of bone, bone-targeting agents that coordinate with calcium or recognize hydroxyapatite (HAp) have been used to deliver drugs or as imaging agents for the therapy and diagnosis of bone-related diseases. To date, various bisphosphonates or acidic oligopeptide-based bone-targeting agents have been explored. However, bisphosphonates can induce osteonecrosis, and acidic oligopeptide-based molecules have not yet been validated in in vivo bone imaging. In this study, we newly designed β-glutamic acid (βE)-based bone-targeting agents by conjugating mono-βE or tri-βE with polyethylene glycol (PEG) labeled with Cy7 dye (termed as βE-PEG-Cy7 or βEEE-PEG-Cy7). In vitro and in vivo studies showed that βEEE-PEG-Cy7 binds more strongly to calcium-containing particles and HAp than βE-PEG-Cy7, leading to a clearer visualization of bone tissues and knee joints. Compared to alendronate conjugated-PEG-Cy7 (ALN-PEG-Cy7) as a positive control, βEEE-PEG-Cy7 has lower binding affinity to both HAp and bone tissues, whereas it showed less cytotoxicity toward osteoblastic-like cells. Although βEEE-PEG-Cy7 has a lower performance of binding affinity to HAp and in vivo bone tissues, we believe that βEEE-PEG-Cy7 with less toxicity can be used as a bone-targeting agent for in vivo bone tissue imaging. © 2022 The Korean Society of Industrial and Engineering Chemistry
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