Primary hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer death worldwide. Alpha-fetoprotein (AFP) has been commonly used as a sensitive tumor marker for the early diagnosis and monitoring of primary HCC. The serum AFP levels for primary HCC patients often increase under conditions such as periods of rapid liver cancer cell growth, relapse and metastasis.

For early stage diagnosis, an AFP level of >15 ng/mL is considered to be an reliable indicator of suspicion of primary HCC, while for monitoring the HCC relapse, the AFP level in the serum usually decreases to <20 ng/mL after the resection of HCC for the first 2 months, and a serial increase in the AFP level indicates the recurrence or metastasis of HCC. Therefore, ultrasensitive detection of AFP featured a large linear range will have a significant impact on the theranostics of HCC.

For this purpose, the research groups led by Prof. CHEN Xueyuan and Academician HONG Maochun from Fujian Institute of Research on the Structure of Matter (FJIRSM), Chinese Academy of Sciences, have recently reported a rational core-shell-shell (CSS) design strategy to construct Eu3+-activated NaGdF4:Yb/Tm@NaGdF4:Eu@NaEuF4 CSS NPs functionalized with efficient upconversion luminescence (UCL) and dissolution-enhanced downshifting luminescence (DSL) of Eu3+ for in-vitro tumor marker detection.

By utilizing the CSS NPs as red luminescent nanoprobes, we demonstrated the successful UCL and DSL bioassays of a typical hepatic carcinoma biomarker of AFP in human serum samples.

The UCL bioassay showed a limit of detection (LOD) of AFP down to 20 pg/mL (290 fM) that was the lowest among luminescent bioassays of AFP ever reported and 30-fold improvement relative to that of commercial dissociation-enhanced lanthanide fluoroimmunoassay kit, while the DSL bioassay by employing the identical CSS NPs can serve as a self-referential validation for the reliability and accuracy of the UCL bioassay for AFP detection.

Results of this study have been published as an edge article in Chemical Science by the Royal Society of Chemistry.

Previously, Prof. CHEN’s groups had made a series of relevant progress on the in-vitro biodetection of tumor markers based on lanthanide-doped luminescent nanoprobes.