Fluorescent-Activating Proteins Manipulate Self-Assembly Peptides Trafficking and Intracellular Distribution.

Peptide-based probes and therapeutics are often hindered by lysosomal degradation and stochastic trafficking, which limit their ability to engage specific organelles with precision. Here, we report a self-assembled peptide system incorporating malachite green (MG), engineered to interact with fluorescent-activating proteins (FAPs) for precise regulation of intracellular peptide trafficking and distribution, enabling effective escape from lysosomal processing. By leveraging the specific binding properties of FAPs, our peptide-MG conjugated enables dynamic modulation of subcellular localization, facilitating targeted transport to organelles such as the nucleus, cytoplasm, and outer membrane. Confocal imaging with a fluorescently labeled peptide further revealed that FAP-mediated interactions can reprogram intracellular trafficking pathways. Furthermore, this system affords spatiotemporal control over peptide aggregation and disassembly, highlighting its potential for applications in drug delivery, synthetic biology, and the study of peptide-based cellular processes.