A Biomimetic Membrane-Coated Nanoprobe for the Ratiometric Fluorescence Detection of Phospholipase A₂

Phospholipase A₂ (PLA₂) is a critical biomarker of many diseases. Among various fluorescent probes, the ratiometric ones have shown great promise because they can provide built-in calibration to avoid interference from analyte-independent factors by simultaneously monitoring two or more fluorescence peaks. Herein, we develop a biomimetic membrane-coated ratiometric fluorescent nanoprobe for the detection of PLA₂. In this design, silica nanoparticles modified with fluorescein isothiocyanate (FITC) are functionalized with a layer of biomimetic membrane that is loaded with Dil dye. Therefore, when the nanocomposite is illuminated by 488 nm incident light, in addition to the fluorescence of FITC centered at 522 nm, that of Dil peaked at 568 nm originating from the energy transfer from FITC to Dil can also be monitored, forming a ratiometric fluorescent nanoprobe. When the target PLA₂ is added, FITC and Dil will no longer be in close proximity because it hydrolyzes the biomimetic membrane, cutting off the energy flow between the two dyes. Consequently, the ratiometric fluorescent signal of the nanoprobe is altered to quantitatively reflect the content of PLA₂. This study provides an effective approach to PLA₂ detection, and the biomimetic membrane-mediated ratiometric design is promising in developing a new generation of biosensors.