Molecular Self-Assembly of Peptides into Supramolecular Nanoarchitectures for Target-Specific Drug Delivery

Self-assembled fluorescent peptides are promising drug-delivery vehicles targeting cancer cells and enhancing the precision of therapeutic agents. Several systems have been developed including fluorescent peptides as cysteine-core peptides, cyclic peptides, nanostructures and peptide polymer conjugates specifically designed for targeted drug delivery. Further, these supramolecular carriers aid in targeted drug transport by using different cargos like doxorubicin (Dox), paclitaxel (PTX), etc. Additionally, dipeptides such as tryptophan-phenylalanine self-assemble via zinc ion chelation, facilitating the endosomal escape thereby enhancing the drug efficacy within multifunctional nanoparticle systems. Furthermore, pH-activatable and enzyme-responsive peptide nanostructures have been engineered to exhibit potential for controlled drug release. These self-assembled peptide systems not only enable targeted drug delivery but also provide controlled release, with applications extending to ocular drug delivery and the treatment of retinal diseases. These systems possess intrinsic fluorescence properties that allow real-time tracking of drug release and cellular uptake, making them highly useful for theranostic applications. Moreover, fluorescently tagged cell-penetrating peptides (CPPs) are widely used to explore how these systems enter cells, revealing multiple ways they are taken up, like endocytosis, micropinocytosis, direct membrane crossing, and counterion-assisted transport. This versatility adds real value to peptide-based approaches in cancer therapy. Further research advancements should enhance stability, explore combination therapies, and improve clinical translation for broader therapeutic applications.