Targeting Fluorescent Nanodiamonds to Vascular Endothelial Growth Factor Receptors in Tumor

Abstract

The increased expression of vascular endothelial growth factor (VEGF) and its receptors is associated with angiogenesis in a growing tumor, presenting potential targets for tumor-selective imaging by way of targeted tracers. Though fluorescent tracers are used for targeted in vivo imaging, the lack of photostability and biocompatibility of many current fluorophores hinder their use in several applications involving long-term, continuous imaging. To address these problems, fluorescent nanodiamonds (FNDs), which exhibit infinite photostability and excellent biocompatibility, were explored as fluorophores in tracers for targeting VEGF receptors in growing tumors. To explore FND utility for imaging tumor VEGF receptors, we used click-chemistry to conjugate multiple copies of an engineered single-chain version of VEGF site-specifically derivatized with trans-cyclooctene (scVEGF-TCO) to 140 nm FND. The resulting targeting conjugates, FND-scVEGF, were then tested for functional activity of the scVEGF moieties through biochemical and tissue culture experiments and for selective tumor uptake in Balb/c mice with induced 4T1 carcinoma. We found that FND-scVEGF conjugates retain high affinity to VEGF receptors in cell culture experiments and observed preferential accumulation of FND-scVEGF in tumors relative to untargeted FND. Microspectroscopy provided unambiguous determination of FND within tissue by way of the unique spectral shape of nitrogen-vacancy induced fluorescence. These results validate and invite the use of targeted FND for diagnostic imaging and encourage further optimization of FND for fluorescence brightness.

Transferrin‐Coated Nanodiamond–Drug Conjugates for Milliwatt Photothermal Applications

“…Tracking of particles in real time over long periods can reveal information about biodistribution whereas the defect centers (e.g., NV − , Si) enable sensing of temperature as a nanoscale thermometer to monitor photothermal effects in situ. To date, nanodiamonds have already been applied successfully in vivo for many animal models (mouse, chicken embryo, and miniature pig)…”

“…Hence, the capability to chemically introduce novel functions tends to be severely hampered by the aggregation of the NDs. To alleviate this primary issue, nanodiamond coating technologies have been developed using adsorption mechanisms deriving from weak attractive forces (electrostatic, van der Waals, hydrogen bonding) and/or strong covalent interactions . However, these coating technologies have persistent difficulties due to batch to batch production variability impacting the surface composition of NDs.…”

Nanodiamenty: unikalne nanocząsteczki do zastosowania w biomedycynie i biotechnologii

“…human epidermal growth factor receptor), bewacizumab hamujący neowasculogenezę nowotworową przez wiązanie z czynnikiem wzrostu śródbłonka naczyniowego (VEGF, ang. vascular endothelial growth factor) oraz edrekolomab skierowany przeciwko antygenowi 17-1A charakterystycznemu dla komórek nowotworowych przewodu pokarmowego [130][131][132].…”

Targeting Nanodiamonds to the Nucleus in Yeast Cells

“…Targeting fluorescent nanodiamonds has been done for mostly cancer/tumor diagnostic applications [ 24 , 27 ]. As a first, we have been able to achieve targeting in Saccharomyces cerevisiae (yeast cells).…”