Histidine-Based Carbon Dots for Bioimaging of Lipid Vesicles

Abstract Carbon dots (CDs) with tunable emission properties are highly sought after for bioimaging and white-light-emitting applications; however, achieving distinct emission from a single-precursor system remains challenging. This limitation arises, in part, from an incomplete understanding of how subtle variations in synthesis conditions dictate nanoscale organization and, consequently, regulate interactions at biologically relevant interfaces. Herein, we report a pH-mediated synthesis of histidine-derived carbon dots (His-CDs) at pH < 1 (His-CD1) and pH 8 (His-CD8), which exhibit distinct photophysical properties. The variation in photoluminescence is attributed to the coexistence of aggregated and nonaggregated species in His-CD1, whereas His-CD8 predominantly comprises relatively uniform, nonaggregated particles with distinct surface functionalities. These structural differences lead to contrasting lipid membrane interactions: His-CD1 preserves the liposomal morphology and embeds within the bilayer, whereas His-CD8 induces liposome aggregation. This selective behavior is governed by particle size, amphiphilicity, electrostatic interactions, and hydrogen bonding, which collectively determine the affinity and modes of interaction with the lipid bilayers. Beyond biointerface relevance, His-CD1 further enables tunable emission from cool to warm white light upon incorporation into polymer matrices. Overall, this study can serve as a unified framework linking synthesis conditions, aggregation states, optical responses, and membrane interactions of CDs. These insights can advance the fundamental understanding of CD-biomembrane interactions and provide a rational design basis for next-generation carbon dot-based probes for lipid bioimaging and efficient white-light-emitting materials.