Triplet Energy Transfer-Sensitized NIR-II Luminescent Nanoprobes for Ultrasensitive Detection of Prostate-Specific Antigen

Abstract

The ultrasensitive detection of prostate-specific antigen (PSA) remains challenging for therapeutic evaluation and management of prostate cancer, particularly in monitoring post-prostatectomy recurrence. Current immunoassays, however, lack the sensitivity and robustness necessary for detecting trace-level PSA in clinical samples. To address this limitation, we develop a triplet energy transfer (TET)-sensitized downshifting luminescence immunosorbent assay (TET-DLISA) platform by utilizing size-optimized NaGdF₄:Yb³⁺/Er³⁺ downshifting nanoparticles (DSNPs) functionalized with a carboxylated near-infrared dye (Cypate) as signal reporters, for background-free NIR-II detection. Under 808-nm excitation, efficient TET from Cypate to Yb³⁺ amplifies the NIR-II emission of Er³⁺ by 284 times in 5.8-nm DSNPs, achieving a highly enhanced intersystem crossing efficiency (82.8%) while minimizing interfacial energy loss. By introducing DSNP@Cypate as an NIR-II signal reporter, the proposed TET-DLISA enables ultrasensitive PSA quantification via alkaline phosphatase (ALP)-catalyzed phosphate displacement of Cypate, yielding an outstanding signal-to-background ratio (SBR) of 273 and a detection limit of 98 fg mL⁻¹, which is three orders of magnitude more sensitive than the corresponding ALP-based ELISA. Clinical validation with patient sera confirms a strong correlation with the results from commercial kits, demonstrating the platform's clinical utility for post-surgical monitoring. This TET-DLISA platform provides a transformative paradigm for ultrasensitive biomarker detection, addressing unmet needs in precision diagnostics.

Keywords

lanthanide-doped nanoparticles / NIR-II luminescence / prostate-specific antigen / triplet energy transfer / ultrasensitive detection

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2025 The Author(s). Aggregate published by SCUT, AIEI, and John Wiley & Sons Australia, Ltd.