A Peptide-Derived Aggregation-Induced Emission Nanobioprobe: Unlocking Selective Detection of Fusobacterium nucleatum and Noninvasive Screening of Colorectal Cancer

Abstract

Colorectal cancer (CRC) screening and early diagnosis is an effective strategy for reducing CRC mortality. However, the current detection methods involve exorbitant costs and complex procedures, which are inconvenient for large-scale screening. Given its high prevalence in malignant tissues and feces of CRC patients, Fusobacterium nucleatum (F. nucleatum) has emerged as a crucial biomarker for the early detection of CRC. Herein, we propose an F. nucleatum-specific recognition strategy for CRC screening and diagnosis. A novel nanobioprobe (AIE-Pep) with aggregation-induced emission (AIE) characteristics was synthesized by conjugating a red/near-infrared (NIR) emissive AIE luminogen (AIEgen) with a FadA-targeting peptide (ASANWTIQYND). The robust binding affinity between the peptide and FadA on F. nucleatum allows AIE-Pep NPs to adhere selectively to F. nucleatum, and emits strong red/NIR fluorescence. In the model of the orthotopic CRC, AIE-Pep NPs can precisely localize F. nucleatum around CRC. Moreover, AIE-Pep NPs demonstrated a limit of detection (LOD) of 82.97 CFU/mL for F. nucleatum, which could significantly differentiate the feces of CRC mice from those of normal mice. Overall, this study presents a pivotal approach to specifically identifying F. nucleatum and holds immense potential for CRC diagnosis.

Keywords

aggregation-induced emission / Fusobacterium nucleatum / colorectal cancer / bacterial recognition / adhesin FadA

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