Engineering disease analyte response in peptide self-assembly

A need to enhance the precision and specificity of therapeutic nanocarriers inspires the development of advanced nanomaterials capable of sensing and responding to disease-related cues. Self-assembled peptides offer a promising nanocarrier platform with versatile use to create precisely defined nanoscale materials. Disease-relevant cues can range from large biomolecules, such as enzymes, to ubiquitous small molecules with varying concentrations in healthy versus diseased states. Notably, pH changes (i.e., H⁺ concentration), redox species (e.g., H₂O₂), and glucose levels are significant spatial and/or temporal indicators of therapeutic need. Self-assembled peptides respond to these cues by altering their solubility, modulating electrostatic interactions, or facilitating chemical transformations through dynamic or labile bonds. This review explores the design and construction of therapeutic nanocarriers using self-assembled peptides, focusing on how peptide sequence engineering along with the inclusion of non-peptidic components can link the assembly state of these nanocarriers to the presence of disease-relevant small molecules.