A novel fluorescent digitonin derivative for non-invasive skin cholesterol detection: potential application in atherosclerosis screening

Jingshu Ni; Yong Liu; Haiou Hong; Xiangyong Kong; Yongsheng Han; Lei Zhang; Yang Zhang; Yuanzhi Zhang; Changyi Hua; Quanfu Wang; Xia Wang; Yao Huang; Wang YiKun; Dong Meili

doi:10.1039/d2ra01982e

A novel fluorescent digitonin derivative for non-invasive skin cholesterol detection: potential application in atherosclerosis screening

RSC Adv. 2022 Jun 22;12(29):18397-18406. doi: 10.1039/d2ra01982e.

Authors

Jingshu Ni^{1

2}, Yong Liu^{1

2

3}, Haiou Hong⁴, Xiangyong Kong⁴, Yongsheng Han⁴, Lei Zhang⁵, Yang Zhang^{1

2}, Yuanzhi Zhang^{1

3}, Changyi Hua¹, Quanfu Wang¹, Xia Wang¹, Yao Huang^{1

3}, Wang YiKun^{1

3}, Dong Meili^{1

3}

Affiliations

¹ Anhui Provincial Engineering Technology Research Center for Biomedical Optical Instrument, Anhui Provincial Engineering Laboratory for Medical Optical Diagnosis &Treatment Technology and Instrument, Anhui Institute of Optics and Fine Mechanics, Hefei Institutes of Physical Science, Chinese Academy of Sciences Hefei 230031 China dongmeili@aiofm.ac.cn wyk@aiofm.ac.cn.
² University of Science and Technology of China Hefei 230026 China.
³ Wanjiang Center for Development of Emerging Industrial Technology Tongling 244000 China.
⁴ The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001 China.
⁵ Anhui Provincial Institute for Food and Drug Control Hefei 230051 China.

Abstract

There is a great demand for the rapid and non-invasive atherosclerosis screening method. Cholesterol content in the epidermis of the skin is an early biomarker for atherosclerosis. Risk assessment of atherosclerosis can be achieved by measuring cholesterol in the epidermis. Here, we synthesised a new fluorescent digitonin derivative (FDD) for the non-invasive detection of skin cholesterol. The results of fluorescence spectroscopy studies indicated that the probe exhibited desirable selectivity for cholesterol. The proof-of-concept preclinical study confirmed that FDD can detect different concentrations of skin cholesterol; patients diagnosed with atherosclerotic cardiovascular disease and the at-risk atherosclerosis group exhibited higher skin cholesterol content than the normal group. The area under the ROC curve for distinguishing the normal/disease group was 0.9228 (95% confidence interval, 0.8938 to 0.9518), and the area under the ROC curve for distinguishing the normal/risk group was 0.9422 (95% confidence interval, 0.9178 to 0.9665). We anticipate that this non-invasive skin cholesterol test may be used as a risk assessment tool for atherosclerosis screening in a large population for further examination and intervention in high-risk populations.