image: Pomegranate-like lanthanide nanoprobes with strong single-particle luminescence and long photoluminescence lifetime were developed for ultrasensitive cancer biomarker detection and visual discrimination of cancer cells.
Credit: ©Science Bulletin
Early cancer detection is critical to improving patient survival rates worldwide, yet the low abundance of cancer biomarkers in human body fluids poses a major barrier to precise early diagnosis. Lanthanide (Ln3+)-doped fluoride nanoprobes have evoked considerable interest in the detection of cancer biomarkers due to their distinctive optical features. Boosting the luminescence of Ln3+-doped fluoride bioprobes can improve the signal-to-noise ratio, which is critical for realizing ultrasensitive detection.
Xueyuan Chen and colleagues, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, proposed a facile in situ enrichment strategy to improve the single-particle photoluminescence (PL) performance of lanthanide bioprobes by confining the growth of numerous CeF3:Tb NPs in dendritic mesoporous silica (DMS) nanospheres. The resulting water-soluble silica-lanthanide fluoride (DMS-CeF3:Tb) nanocomposites exhibited intense single‑particle luminescence, a high PL quantum yield of 22.9%, and an exceptionally long PL lifetime of 2.7 milliseconds, which enables background‑free time‑resolved PL (TRPL) detection. Moreover, the nanoprobes maintain stable luminescence across a wide pH range (2.5–8.0) and in simulated human body fluid, along with favorable cytocompatibility, ensuring reliable performance in complex physiological environments.
Leveraging their flexible surface functionalization capability, the research team modified DMS-CeF3:Tb nanoprobes with biotin to target biotin receptors overexpressed on cancer cell surfaces. Confocal imaging confirmed that biotinylated nanoprobes can specifically bind to human cervical cancer (HeLa) cells and produce bright green luminescence. The TRPL signal intensity of cancer cell-probe complexes was 4.3-fold higher than that of normal cell groups, realizing rapid, low-cost cell-level cancer screening.
Beyond visual cancer cell identification, the team further constructed a high-performance TRPL immunoassay platform using avidin-conjugated DMS-CeF3:Tb nanoprobes for quantitative detection of cancer biomarker prostate specific antigen (PSA). The optimized biosensor delivers an unprecedented limit of detection (LOD) of 41 fg mL-1, which is 215-fold lower than that of pure CeF3:Tb nanoprobes and 976-fold lower than that of a commercial PSA enzyme-linked immunosorbent assay (ELISA) kit.
In clinical validation tests covering 33 human serum samples, the DMS-CeF3:Tb nanoprobe-based detection method achieved excellent consistency with the hospital’s clinical electrochemiluminescence immunoassay (ECLIA), with a correlation coefficient of 0.997. Additionally, the platform exhibited outstanding analytical accuracy and precision, with serum sample recovery rates ranging from 95% to 110% and coefficients of variation below 10%, fully meeting clinical bioanalytical standards. The versatile nanoprobe system can also be adapted for the detection of other critical cancer biomarkers such as alpha-fetoprotein (AFP) via simple antibody substitution.
“We anticipate that such enrichment-enhanced luminescent nanoprobes will help address the challenges of visual cancer cell discrimination and ultrasensitive biomarker detection in body fluids for early clinical cancer screening,” said the research team.