Self‐Assembly of Therapeutic Peptides for Enhanced Cancer Therapy: Strategies, Therapeutic Performance, and Future Perspectives

ABSTRACT Therapeutic peptides have attracted increasing attention for cancer therapy owing to their high biological activity, target specificity, and diverse mechanisms of action, but their clinical application is limited by poor stability and inefficient delivery. Peptide self‐assembly has emerged as a promising peptide delivery strategy that enables therapeutic peptides to organize into well‐defined supramolecular structures through non‐covalent interactions, offering opportunities to improve their delivery performance. This review provides a comprehensive overview of peptide self‑assembly mechanisms, focusing on synergistic non‑covalent interactions and environmental modulation, and summarizes the major assembly strategies for antitumor peptides, including spontaneous self‐assembly of monomers, co‐assembly with functional components, and tumor microenvironment‐responsive assembly. The application of self‐assembly strategies in improving tumor accumulation, tumor retention, intracellular delivery, and antitumor efficacy of antitumor peptides was also discussed. Finally, we highlight the current challenges associated with structural stability, scalable manufacturing, and clinical translation, and propose potential strategies to facilitate clinical translation of self‐assembling peptide therapeutics. Overall, this review provides a systematic framework for the rational design of self‐assembling therapeutic peptides and offers perspectives for the development of next‐generation peptide nanomedicines for cancer therapy.