Fluorescence Detection of Bone Microcracks Using Monophosphonated Carbon Dots

Abstract

Phosphonated compounds, in particular, bisanalogs are widely applied in clinical settings for the treatment of severe bone turnovers and recently as imaging probes when conjugated with organic fluorophores. Herein, we introduce a bone seeking luminescent probe that shows a high binding affinity toward bone minerals based on monophosphonated carbon dots (CDs). Spheroidal CDs tethered with PEG monophosphates are synthesized in a one-pot hydrothermal method and are physicochemically characterized, where the retention of phosphonates is confirmed by P NMR and X-ray photoelectron spectroscopy. Interestingly, the high abundance of multiple monodentate phosphonates exhibited strong binding to hydroxyapatite, the main bone mineral constituent. The remarkable optophysical properties of monophosphonated CDs were confirmed in an ex vivo model of the bovine cortical bone where the imaging feasibility of microcracks, which are calcium-rich regions, was demonstrated. The in vivo studies specified the potential application of monophosphonated CDs for imaging when injected intramuscularly. The biodigestible nature and cytocompatibility of the probe presented here obviate the demand for a secondary fluorophore, while offering a nanoscale strategy for bone targeting and can eventually be employed for potential bone therapy in the future.

Bone Tissue Engineering via Carbon‐Based Nanomaterials

“…The fluorescence of C‐dots can be utilized for the detection of the bone microcracks. Reproduced with permission . Copyright 2018, American Chemical Society.…”

“…Healthcare Mater. 2020, 9,1901495 C-dots GA e) ----Bone crack detection [246,247] C-dots ---Mice Bone crack detection [249] C-dots ----Zebrafish Bone targeting [253] C-dots ----Zebrafish Targeted bone imaging and drug delivery [254,255] a) CaPs: calcium Phosphate; GA: glutamic acid; HA: hydroxyapatite; PLLA: poly (L-lactic acid); b) hMSCs: human mesenchymal stem cells; rMSCs: rat mesenchymal stem cells; c) B⇧: bone regeneration enhancement; Me⇧: mechanical strength enhancement; Mi⇧: mineralization promotion; O⇧: cell osteogenic differentiation promotion; P⇧: cell proliferation increase; d) C-dots were covalently conjugated with bone-promotion peptides; e) GA was covalently conjugated onto C-dots.…”

“…Reproduced with permission. [249] Copyright 2018, American Chemical Society. C) Schematic illustration of (C1) fluorescence imaging via the specific affinity of Alen-C-dots towards calcium-deficient HA scaffolds (in vitro), rat femur (ex vivo), and live zebrafish (in vivo) and (C2) the preparation and bone affinity of Alen-C-dots and Alen-EDA-C-dots.…”

“…The high affinity of mono‐phosphonate towards Ca 2+ and HA enabled the probe to detect bone micro cracks in both ex vivo and in vivo models (Figure 18B). Although these systems exhibit high biocompatibility and excellent bone tracking capability, significant surface modifications on C‐dots are generally required to integrate functionalities (i.e., glutamic acid, mono‐phosphonate) for bone crack detection. These surface modifications could include tedious multi‐step reactions, treatments, and corresponding separation and purification, which would significantly increase the difficulties in the fabrication of these systems and affect their reproducibility.…”

Carbon Dots Induce Epithelial‐Mesenchymal Transition for Promoting Cutaneous Wound Healing via Activation of TGF‐β/p38/Snail Pathway

“…[10] Carbon dots (CDots) are less than 10 nm carbonbased nano particles with several distinct merits, such as low cytotoxicity, abundant raw material, easy preparation, and fluorescence properties, thus showing great potential in various biomedical applications, including antiinflammation, [29] bacteriostasis, [30] bioimaging [31] and so on. [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47] Meaningfully, through neutral izing the reactive oxygen species from inflammation/infec tion and sterilizing the bacteria in the wounds, CDots could be utilized to accelerate wound healing. [48,49] Despite these achievements, however, only the contaminated and dirty infected wounds usually need antibacterial treatment, [50] but a rapid reepithelialization of the wound surface for forming the epidermal barrier is significant in various wounds.…”