Ultrasensitive detection of HPV-associated lower genital tract lesions using a NIR-excited luminescent assay with lanthanide-doped upconversion nanoprobes and enzymatic digestion protection

  • Talanta. 2026 Jun 12:310:130139. doi: 10.1016/j.talanta.2026.130139.
Wuchao Chen  1 Xiaobo Gu  2 Liangzhi Cai  3 Jingwen Tang  4 Xiaodong Yi  2 Xiaoying Shang  2 Xingyang Liu  2 Yuxiang Zhang  4 Lei Zhang  5 Zhuo Chen  6
Affiliations
  • 1. State Key Laboratory of Structural Chemistry, Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian, 350108, China; Fujian Agriculture and Forestry University, Fuzhou, Fujian, 350002, China.
  • 2. State Key Laboratory of Structural Chemistry, Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian, 350108, China.
  • 3. Department of Gynecology, Fujian Provincial Maternity and Child Health Hospital, Fuzhou, Fujian, 350001, China; College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, Fujian, 350122, China. Electronic address: [email protected].
  • 4. State Key Laboratory of Structural Chemistry, Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian, 350108, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
  • 5. State Key Laboratory of Structural Chemistry, Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian, 350108, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Structural Chemistry, Key Laboratory of Optoelectronic Materials Chemistry and Physics, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fujian Academy, University of Chinese Academy of Sciences, Fuzhou, Fujian, 350108, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: [email protected].
Abstract

Persistent high-risk human papillomavirus (HPV) Infection is a major cause of cervical carcinogenesis, yet current diagnostic methods - particularly colposcopy with nonspecific dyes - lack the precision needed for early-stage precancerous lesion detection. To address this gap, we developed a luminescent nanoprobe platform based on lanthanide-doped upconversion nanocrystals for HPV E7 oncoprotein detection, featuring three key advancements: (1) The nanoprobes exploit long luminescence lifetimes and near-infrared (NIR) emission to minimize background autofluorescence and enhance tissue penetration, while epitope -specific binding to E7 antigens ensures high target selectivity. (2) A homogeneous detection scheme, defined as the final solution-phase fluorescence reading obtained after proteolytic digestion, wherein proteolysis triggers Cell Lysis and probe release, enables precise fluorescent signal acquisition with a detecting limit of 5 cells/well, while preserving probe integrity for potential reuse. (3) A multichannel targeted imaging strategy suppresses tissue scattering artifacts, significantly improving early-stage lesion detection rates (p < 0.001). This work establishes a novel HPV diagnosis platform with enhanced sensitivity and clinical detection performance.

Keywords
Cervical carcinogenesis; E7 protein; Fluorescent probes; Human papillomavirus (HPV) infection; Lanthanides.