Plasmonic Colorimetric Biosensor for Sensitive Exosome Detection via Enzyme-Induced Etching of Gold Nanobipyramid@MnO₂ Nanosheet Nanostructures

Abstract

Exosomes involved in tumor-specific processes display excellent potential in the early diagnosis of cancer. Herein, a highly sensitive plasmonic colorimetric biosensor was proposed for exosome quantification. The sensing strategy mainly includes two steps: exosome-triggered competitive reaction and etching of gold nanobipyramid@MnO₂ nanosheet nanostructures (Au NBP@MnO₂ NSs). A competitive reaction between exosomes and placeholder chains induced by exosomes can translate the signal of exosomes into the amount of alkaline phosphatase, which simplifies the experimental process and amplifies the signal. The etching of Au NBP@MnO₂ NSs by ascorbic acid generated from the hydrolysis of l-ascorbic acid 2-phosphate by alkaline phosphatase changes the refractive index of Au NBPs, accompanied by the blue shift of the longitudinal localized surface plasmon resonance peak. Profiting from the signal amplification of the competitive reaction and superior refractive index sensitivity of colorimetric substrates, this protocol exhibits high sensitivity toward exosomes within 8.5 × 10² to 8.5 × 10⁴ particles μL^-1, along with a detection limit of 1.35 × 10² particles μL^-1, which is more sensitive than previously reported colorimetric methods. In addition, a sensitive multicolor visual detection of exosomes was realized by adjusting the aspect ratio of Au NBPs. It is worth mentioning that the Au NBP@MnO₂ NSs was synthesized through in situ growth of MnO₂ nanosheets on Au NBPs, and the attractive optical properties and ease of etching make Au NBP@MnO₂ NSs promising candidates for plasmonic detection.