A Host–Guest Interaction-Based and Metal–Organic
Gel-Based Biosensor with Aggregation-Induced Electrochemiluminescence
Enhancement for Methyltransferase Assay
Metal–organic
gels (MOGs) are new soft materials with the
characteristics of high colloidal stability, superb luminescence properties,
and facile synthesis. Herein, we develop for the first time a host–guest
interaction-based and MOG-based biosensor with aggregation-induced
electrochemiluminescence (ECL) enhancement for M.SssI methyltransferase
(M.SssI MTase) assay. This biosensor employs a MOG as the luminophor
and potassium persulfate as the coreactant, and the formation of the
Ag-MOG from the aggregation of silver nanoclusters can induce significant
ECL enhancement. Two complementary single-stranded DNAs (ssDNAs, i.e.,
biotinylated DNA-1 and Fc-labeled DNA-2) that contain specific recognition
sequence 5′-CCGG-3′ can form a double-stranded DNA (dsDNA)
probe. In the absence of M.SssI MTase, the dsDNA probe will be digested
by restriction endonuclease HpaII, leading to the release of Fc from
magnetic beads (MBs). The β-CD can specifically recognize the
released Fc through guest–host interaction, resulting in the
quenching of an ECL signal. In contrast, the presence of M.SssI MTase
enables the formation of fully methylated dsDNA, which cannot be cleaved
by HpaII, making Fc remain on the MB surface and consequently generating
an improved ECL signal. This biosensor can specifically detect M.SssI
MTase with a linear range of 0.05–100 U mL–1 and a limit of detection of 3.5 × 10–3 U
mL–1, and it enables accurate detection of M.SssI
MTase in human serum. In addition, it can be used for inhibitor screening,
with wide applications in drug discovery and disease diagnosis.