Self-assembled peptide delivery systems: Applications in tumor therapy

Self-assembled peptides are emerging as versatile nanocarriers for cancer therapy, benefiting from programmable sequences, biocompatibility, and dynamic supramolecular assembly. This review summarizes recent advances in the molecular design and assembly mechanisms of peptide-based nanostructures (nanospheres, nanofibers, and nanogels) formed through non-covalent interactions, such as hydrogen bonding, electrostatics, van der Waals forces, and π-π stacking. We discuss how peptide composition, secondary structure, and environmental cues (pH, enzymes, redox state, temperature, and ionic strength) govern assembly, stability, and biological performance, enabling efficient loading and targeted delivery of small-molecule drugs, nucleic acids (DNA/small interfering RNA), and peptide or protein therapeutics. Particular emphasis is placed on stimuli-responsive strategies and in situ assembly approaches that enable controlled drug release and, where applicable, provide imaging readouts (fluorescence, photoacoustic, and nuclear imaging) for tumor visualization, image-guided delivery, and treatment-response monitoring. Key translational challenges are also addressed, including serum stability and pharmacokinetics, immunogenicity and off-target effects, endosomal escape and delivery efficiency, scalable manufacturing and cost, controllability of release, and standardized characterization and safety evaluation. Finally, we outline future directions, including multifunctional and smart responsive peptide architectures, hybrid systems combining peptides with liposomes, polymers, or viral vectors, and rational design rules linking assembly state to in vivo fate. Collectively, these advances are expected to accelerate the clinical translation of self-assembled peptide delivery systems for precision cancer therapy.