Noninvasive In Situ Ratiometric Imaging of Biometals Based on Self-Assembled Peptide Nanoribbon

Abstract

Development of probes for accurate sensing and imaging of biometals in situ is still a growing interest owing to their crucial roles in cellular metabolism, neurotransmission, and apoptosis. Among them, Zn²⁺ and Cu²⁺ are two important cooperative biometals closely related to Alzheimer's disease (AD). Herein, we developed a multifunctional probe based on self-assembling peptide nanoribbon for ratiometric sensing of Zn²⁺, Cu²⁺, or Zn²⁺ and Cu²⁺ simultaneously. Uniform peptide nanoribbon (AQZ@NR) was rationally designed by coassembling a Zn²⁺-specific ligand AQZ-modified peptide (AQZKL-7) with peptide KL-7. The nanoribbon further combined with Cu²⁺-sensitive near-infrared quantum dots (NIR QDs) and Alexa Fluor 633 as an inner reference molecule, which was endowed with the capability for ratiometric Zn²⁺ and Cu²⁺ imaging at the same time. The peptide-based probe exhibited good specificity to Zn²⁺ and Cu²⁺ without interference from other ions. Importantly, the nanoprobe was successfully applied for noninvasive Zn²⁺ and Cu²⁺ monitoring in both living cells and zebrafish via multicolor fluorescence imaging. This gives insights into the dynamic Zn²⁺ and Cu²⁺ distribution in an intracellular and in vivo mode, as well as understanding the neurotoxicity of high concentration of Zn²⁺ and Cu²⁺. Therefore, the self-assembled nanoprobe shows great promise in multiplexed detection of many other biometals and biomolecules, which will benefit the diagnosis and treatment of AD in clinical applications.