PLK1-Targeted Fluorescent Tumor Imaging with High Signal-to-Background Ratio.
Ji-Ting HouKyung-Phil KoHu ShiWen Xiu RenPeter VerwilstSeyoung KooJin Yong LeeSung-Gil ChiJong Seung KimPublished in: ACS sensors (2017)
As significantly expressed during cell division, polo-like kinase 1 (PLK1) plays crucial roles in numerous mitotic events and has attracted interest as a potential therapeutic marker in oncological drug discovery. We prepared two small molecular fluorescent probes, 1 and 2, conjugated to SBE13 (a type II PLK1 inhibitor) to investigate the PLK1-targeted imaging of cancer cells and tumors. Enzymatic docking studies, molecular dynamics simulations, and in vitro and in vivo imaging experiments all supported the selective targeting and visualization of PLK1 expressing cells by probes 1 and 2, and probe 2 was successfully demonstrated to image PLK1-upregulated tumors with remarkable signal-to-background ratios. These findings represent the first example of small-molecule based fluorescent imaging of tumors using PLK1 as a target, which could provide new avenues for tumor diagnosis and precision therapeutics.
Keyphrases
- small molecule
- molecular dynamics simulations
- living cells
- high resolution
- quantum dots
- drug discovery
- protein protein
- fluorescence imaging
- cancer therapy
- single molecule
- induced apoptosis
- fluorescent probe
- stem cells
- single cell
- deep learning
- cell therapy
- hydrogen peroxide
- drug delivery
- oxidative stress
- cell cycle
- radical prostatectomy
- rectal cancer
- cell death