Selective Sensing of Lactate Dehydrogenase A by Naphthalene Diimide-Based AIEgen as a Diagnostic Probe toward Cancer...

Fluorescent organic nanoparticles (FONPs), exhibiting aggregation-induced emission (AIE), are emerging as superior sensors due to their easy fabrication, versatility, and biocompatibility. The present article delineates the detection of lactate dehydrogenase A (LDHA) by exploiting the AIE property of synthesized naphthalene diimide (NDI)-based amphiphile comprising an aromatic (Ar-Py-1, Ar-Py-2) and aliphatic (Al-Py) pyruvate moieties. Elevated expression of LDHA in cancer cells plays a crucial role in cancer progression through increased conversion of pyruvate to lactate. Self-aggregated spherical organic nanoparticles were constructed by NDI derivatives with a diameter of ∼100-200 nm through J-aggregation in DMSO-water (f_w = 99 vol %). Ar-Py-1 exhibited AIE in the greenish-blue region (λ_max ∼487 nm), while Ar-Py-2 and Al-Py (containing naphthyl residue) exhibited AIE in the orange region via intramolecular charge transfer from naphthyl to the NDI core, having λ_max ∼ 590 nm. Al-Py FONPs were found to be an excellent probe for sensing LDHA through an AIE-based "fluorescence off'' mechanism by its enzymatic reduction. Fluorescence intensity of Al-Py FONPs gradually got quenched in response to LDHA due to the conversion of fluorescent pyruvate to non-fluorescent lactate, having a limit of detection of ∼18.6 ng mL^-1. LDHA sensing by Al-Py FONPs was found to be highly selective against other biomolecules and enzymes. Al-Py FONPs were successfully utilized toward selective diagnosis of cancer cells (MDA-MB-231 and MCF-7) over normal cells (HEK 293) through quenching of their fluorescence by overexpressed LDHA within cancer cells. Therefore, Al-Py FONPs emerged as a diagnostic biomarker for selective and sensitive detection of LDHA by ministering their AIE property.